La hiperactividad y el empuje de la civilización

La clínica y el trabajo en las instituciones nos muestran cambios dramáticos en la subjetividad contemporánea. Las personas se encuentran expuestas a demandas sociales que tienen consecuencias funestas sobre ellas. Y que se manifiestan en grados diversos de hiperactividad, o actividad compulsiva, hasta el colapso subjetivo bajo la forma de depresión o irrupciones masivas de angustia. En los niños se verifica desde hace un tiempo un fenómeno al que se le ha dado un nombre Trastorno por Déficit Atencional con Hiperactividad, y cuyo tratamiento se confía al uso paradójico de estimulantes. En este artículo se relacionan las causas de este fenómeno, con las modalidades culturales que propician el reemplazo de la experiencia subjetiva por protocolos de acción predeterminados.The clinical practice and work in the institutions show us dramatic changes in contemporary subjectiveness. People find themselves exposed to social demands with harmful consequences. These consequences become evident through different degree of hyperactivity or compulsive activity, until the subject collapses in forms of depression or massive incidents of distress. Since a few years ago an exceptional phenomenon has been occurring in children that it has been appointed Attention Deficit Hyperactivity Disorder. Its treatment is based on the paradoxical use of stimulants. In this paper the causes of this phenomenon and the cultural patterns that help the displacement of the subjective experience by predetermined protocols are discussed.Fil: Tuñón, José Luis. Universidad Nacional de la Patagonia San Juan Bosc

Espiritualidad e inquisición en Asturias en el siglo XVIII: El proceso del Obispo José Fernández de Toro

La investigación realizada profundiza en el estudio de la diócesis de Oviedo en el primer tercio del siglo XVIII, un periodo escasamente abordado por la historiografía. Analiza el complejo y controvertido episcopado ovetense de José Fernández de Toro, tardío pero significativo exponente de la difusión alcanzada en España por Miguel de Molinos y su Guía Espiritual. Estudia minuciosamente y saca a la luz el singular, y prácticamente inédito, proceso inquisitorial seguido contra el obispo ovetense tanto en España como en Roma, cuya resonancia social y transcendencia eclesial se manifestó también en las tensas relaciones hispano-romanas durante la Guerra de Sucesión. Estudia y valora asimismo la repercusión que sus ideas espirituales y comportamientos molinosistas tuvieron en la diócesis ovetense, describiendo la realidad socio-eclesial que caracterizó a Asturias en el período inmediato al movimiento ilustrado. Estudio que pretende poner de manifiesto como el obispo José Fernández de Toro y su relevante proceso inquisitorial constituyen un singular y significativo testimonio de la realidad socio-política española que caracterizó los inicios del reinado de Felipe V, las relaciones diplomáticas mantenidas con la Santa Sede, condicionadas por el posicionamiento del papado respecto a los pretendientes al trono de España, las teorías y doctrinas que inspiraron las relaciones entre el Estado y la Iglesia en la Edad Moderna, la situación de la Inquisición española, sus luchas y diferencias con la práctica inquisitorial romana, así como del panorama espiritual que caracterizó el tránsito de la época barroca a la Ilustración. La tesis se estructura partiendo de una introducción general, justificando los objetivos de la investigación y su importancia. Examinando asimismo el tratamiento y los resultados que hasta el momento brindaba la historiografía sobre el caso del obispo Fernández de Toro, a la par que se describe las fuentes documentales que sustentan la investigación. Siguen seis capítulos, en los que se ofrece un panorama general de la espiritualidad católica en los siglos XVI y XVII, describiendo el estado actual de la historiografía al respecto, se aborda la personalidad y trayectoria del personaje en su doble faceta de inquisidor y obispo, se estudia detalladamente y contextualizada eclesial y políticamente el doble proceso inquisitorial seguido en España y Roma, analizando asimismo su repercusión y consecuencias en la vida diocesana ovetense. Mientras que en el apartado de conclusiones se sintetizan los resultados finales de la investigación, valorando la importancia y significación del personaje, así como de sus actuaciones y doctrinas espirituales en la historia eclesiástica ovetense y española. Completa el estudio un apéndice documental, donde se seleccionan diversos textos conforme al triple criterio de que tengan que ver son su persona y actividad espiritual, recojan las acusaciones de que fue objeto o reflejen las doctrinas que sostuvo y por las que fue condenado. Finalmente se hace relación de las fuentes documentales analizadas y de la amplia bibliografía utilizada.Departamento de Historia Moderna, Contemporánea, de América, Periodísmo y Comunicación Audiovisual y Publicida

Non-coronary atherosclerosis: a marker of poor prognosis in patients undergoing coronary artery bypass surgery

IntroductionThe presence of non-coronary atherosclerosis (NCA) in patients with coronary artery disease is associated with a poor prognosis. We have studied whether NCA is also a predictor of poorer outcomes in patients undergoing coronary artery bypass grafting (CABG).Materials and methodsThis is an observational study involving 567 consecutive patients who underwent CABG. Variables and prognosis were analysed based on the presence or absence of NCA, defined as previous stroke, transient ischaemic attack (TIA), or peripheral artery disease (PAD) [lower extremity artery disease (LEAD), carotid disease, previous lower limb vascular surgery, or abdominal aortic aneurysm (AAA)]. The primary outcome was a combination of TIA/stroke, acute myocardial infarction, new revascularization procedure, or death. The secondary outcome added the need for LEAD revascularization or AAA surgery.ResultsOne-hundred thirty-eight patients (24%) had NCA. Among them, traditional cardiovascular risk factors and older age were more frequently present. At multivariate analysis, NCA [hazard ratio (HR) = 1.84, 95% confidence interval (CI) 1.27–2.69], age (HR = 1.35, 95% CI 1.09–1.67, p = 0.004), and diabetes mellitus (HR = 1.50, 95% CI 1.05–2.15, p = 0.025), were positively associated with the development of the primary outcome, while estimated glomerular filtration rate (HR = 0.86, 95% CI 0.80–0.93, p = 0.001) and use of left internal mammary artery (HR = 0.36, 95% CI 0.15–0.82, p = 0.035), were inversely associated with this outcome. NCA was also an independent predictor of the secondary outcome. Mortality was also higher in NCA patients (27.5% vs. 9%, p < 0.001).ConclusionsAmong patients undergoing CABG, the presence of NCA doubled the risk of developing cardiovascular events, and it was associated with higher mortality

Epistolario

Texto curatorial de Patricia Viel (Río Gallegos) y José L. Tuñón (Comodoro Rivadavia), para la muestra Las vidas del arte (artistas, proyectos de artistas y grupos de aristas). Santa Cruz / Chubut, 2014.Este texto se compone de extractos de correos electrónicos entre autores de la muestra: Las vidas del Arte. Fueron enviados desde el 11 de abril al 6 de agosto de 2013, pensando el guion de la muestra que se expuso en el Complejo Cultural Santa Cruz en abril y en el Centro Cultural de Comodoro Rivadavia en agosto de 2014. Los artistas que participan en la muestra son: Sergio Álvarez (Caleta Olivia), César Barrientos (Comodoro Rivadavia), Mariano Britos (Rada Tilly), Í? Poesía Visual: Daniela Mastrandrea (Puerto Madryn), Yamel Najle (Puerto Madryn), Grupo Del Borde: Sonia Cortez, Bettina Muruzabal, Liliana Solari y Andriana Opacak (Río Gallegos), Silvia Ravetta (San Julián), Emanuel Reyes (Puerto Madryn), Daniela y Valeria Valenzuela (Río Gallegos). Curadores: Patricia Viel y José Luis Tuñón.[…]La muestra está marcada por los usos y modos del arte contemporáneo, para bien y para mal. Un criterio diría que su paso ha dejado una considerable libertad en los modos y lugares de la intervención. Otro criterio advertiría acerca del agotamiento de esos procedimientos. Y de nuevo, lo que vitaliza estas prácticas –y cualquier otra– es su relación con un impulso que no es fácil de demostrar, tal vez se pueda volver a hablar simplemente de amor al arte, como en otros tiempos. Por eso Las Vidas Del Arte fue un buen modo de llamarla

Why Are Some Enzymes Dimers? Flexibility and Catalysis in Thermotoga maritima Dihydrofolate Reductase

Dihydrofolate reductase from Thermotoga maritima (TmDFHFR) is a dimeric thermophilic enzyme that catalyzes the hydride transfer from the cofactor NADPH to dihydrofolate less efficiently than other DHFR enzymes, such as the mesophilic analogue Escherichia coli DHFR (EcDHFR). Using QM/MM potentials, we show that the reduced catalytic efficiency of TmDHFR is most likely due to differences in the amino acid sequence that stabilize the M20 loop in an open conformation, which prevents the formation of some interactions in the transition state and increases the number of water molecules in the active site. However, dimerization provides two advantages to the thermophilic enzyme: it protects its structure against denaturation by reducing thermal fluctuations and it provides a less negative activation entropy, toning down the increase of the activation free energy with temperature. Our molecular picture is confirmed by the analysis of the temperature dependence of enzyme kinetic isotope effects in different DHFR enzymes

Unveiling the Mechanistic Singularities of Caspases: A Computational Analysis of the Reaction Mechanism in Human Caspase-1

Caspases are cysteine proteases in charge of breaking a peptide bond next to an aspartate residue. Caspases constitute an important family of enzymes involved in cell death and inflammatory processes. A plethora of diseases, including neurological and metabolic diseases and cancer, are associated with the poor regulation of caspase-mediated cell death and inflammation. Human caspase-1 in particular carries out the transformation of the pro-inflammatory cytokine pro-interleukin-1β into its active form, a key process in the inflammatory response and then in many diseases, such as Alzheimer’s disease. Despite its importance, the reaction mechanism of caspases has remained elusive. The standard mechanistic proposal valid for other cysteine proteases and that involves the formation of an ion pair in the catalytic dyad is not supported by experimental evidence. Using a combination of classical and hybrid DFT/MM simulations, we propose a reaction mechanism for the human caspase-1 that explains experimental observations, including mutagenesis, kinetic, and structural data. In our mechanistic proposal, the catalytic cysteine, Cys285, is activated after a proton transfer to the amide group of the scissile peptide bond, a process facilitated by hydrogen-bond interactions with Ser339 and His237. The catalytic histidine does not directly participate in any proton transfer during the reaction. After formation of the acylenzyme intermediate, the deacylation step takes place through the activation of a water molecule by the terminal amino group of the peptide fragment formed during the acylation step. The overall activation free energy obtained from our DFT/MM simulations is in excellent agreement with the value derived from the experimental rate constant, 18.7 vs 17.9 kcal·mol–1, respectively. Simulations of the H237A mutant support our conclusions and agree with the reported reduced activity observed for this caspase-1 variant. We propose that this mechanism can explain the reactivity of all cysteine proteases belonging to the CD clan and that differences with respect to other clans could be related to the larger preference showed by enzymes of the CD clan for charged residues at position P1. This mechanism would avoid the free energy penalty associated with the formation of an ion pair. Finally, our structural description of the reaction process can be useful to assist in the design of inhibitors of caspase-1, a target in the treatment of several human diseases.The authors thank financial support from grant PID2021-123332OB funded by MCIN/AEI/10.13039/501100011033/ and by “ERDF A way of making Europe” and also from grant PROMETEO CIPROM/2021/079 of Generalitat Valenciana. K.Z. acknowledges a Maria Zambrano fellowship by Ministerio de Universidades (Spain). Computational resources were provided by Barcelona Supercomputing Center and Servei d’Informàtica, Universitat de València (Tirant supercomputer)

Propuesta de un modelo de trabajos prácticos de física en el nivel universitario

We present in this paper a model of practical works in Physics at University level. It has been designed as a result of the research implemented during three years. Our goal has been to achieve a type of practical work according to the educational principles of openness, activity and participation. In this way the students will get used to the scientific methodology closely linked to significative learning

Anencephaly and Severe Myelodysplasia in a Stillborn Brown Bear (Ursus arctos arctos)

[EN] Malformations in the development of the neural tube have been described to be associated with different aetiologies, such as genetic factors, toxic plants, chemical products, viral agents, or hyperthermia. A twenty-four-year-old female Eurasian brown bear (Ursus arctos arctos), permanently in captivity and kept under food and management control, gave birth to a stillborn cub at the end of gestation. Several malformations resulting from the anomalous development of the neural tube, not previously reported in bears, were observed, such as anencephaly, hypoplasia, micromyelia, severe myelodysplasia, syringomyelia, and spina bifida. Multiple canal defects (e.g., absence) were also observed in the spinal cord. In some regions, the intradural nerve roots surrounded the spinal cord in a diffuse and continuous way. The aetiology remains unidentified, although the advanced age of the mother and/or folic acid deficit might have been the possible causes of this disorder. Supplements of folate given to the mother before and during early pregnancy may have reduced the incidence of neural tube defects. That supplementation should be considered when the reproduction of bears is to occur in captivity, in order to prevent the loss of future generations of this endangered speciesSIThis work was partially funded by the Principality of Asturias (PCTI 2021–2023, GRUPIN: IDI-2021-000102) and the European Regional Development Fun