Extracellular cysteine in connexins: Role as redox sensors

Indexación: Scopus.Connexin-based channels comprise hemichannels and gap junction channels. The opening of hemichannels allow for the flux of ions and molecules from the extracellular space into the cell and vice versa. Similarly, the opening of gap junction channels permits the diffusional exchange of ions and molecules between the cytoplasm and contacting cells. The controlled opening of hemichannels has been associated with several physiological cellular processes; thereby unregulated hemichannel activity may induce loss of cellular homeostasis and cell death. Hemichannel activity can be regulated through several mechanisms, such as phosphorylation, divalent cations and changes in membrane potential. Additionally, it was recently postulated that redox molecules could modify hemichannels properties in vitro. However, the molecular mechanism by which redox molecules interact with hemichannels is poorly understood. In this work, we discuss the current knowledge on connexin redox regulation and we propose the hypothesis that extracellular cysteines could be important for sensing changes in redox potential. Future studies on this topic will offer new insight into hemichannel function, thereby expanding the understanding of the contribution of hemichannels to disease progression.http://journal.frontiersin.org/article/10.3389/fphys.2016.00001/ful

Unfolding mechanism and free energy landscape of single, stable, alpha helices at low pull speeds

Single alpha helices (SAHs) stable in isolated form are often found in motor proteins where they bridge functional domains. Understanding the mechanical response of SAHs is thus critical to understand their function. The quasi-static force-extension relation of a small number of SAHs is known from single-molecule experiments. Unknown, or still controversial, are the molecular scale details behind those observations. We show that the deformation mechanism of SAHs pulled from the termini at pull speeds approaching the quasi-static limit differs from that of typical helices found in proteins, which are stable only when interacting with other protein domains. Using molecular dynamics simulations with atomistic resolution at low pull speeds previously inaccessible to simulation, we show that SAHs start unfolding from the termini at all pull speeds we investigated. Unfolding proceeds residue-by-residue and hydrogen bond breaking is not the main event determining the barrier to unfolding. We use the molecular simulation data to test the cooperative Sticky Chain model. This model yields excellent fits of the force-extension curves and quantifies the distance, xE = 0.13 nm, to the transition state, the natural frequency of bond vibration, ν0 = 0.82 ns−1, and the height, V0=2.9 kcal/mol, of the free energy barrier associated with the deformation of single residues. Our results demonstrate that the Sticky Chain model could advantageously be used to analyze experimental force-extension curves of SAHs and other biopolymers

Effects of successive judo matches on interlimb asymmetry and bilateral deficit

Objective: To verify the effects of successive judo matches on interlimb asymmetry and bilateral deficit in judo athletes. Design: Repeated measures Setting: University Judo center Participants: Fourteen male judo athletes Outcome measures: Four simulated matches consisting of 4-min. Before the first match and after each match athletes were submitted to single leg tests – Countermovement Jump (SLCMJ) and Standing Long Jump (SLSLJ), and handgrip strength (HGS) in the dominant and non-dominant limbs. Interlimb asymmetry was calculated in both jumps and handgrip strength tests. Results: Most jump-derived variables did not change the magnitude of asymmetry throughout the matches (p>0.05), with the exception of jump height asymmetry in SLCMJ, that increased after the second match (p=0.001). The HGS decreased in both hands from the first match (p<0.001), without asymmetry. The highest bilateral strength deficit was observed in post-match 1 and post-match 2 (close to 10%). Conclusion: Four-successive judo matches did not change the magnitude of interlimb asymmetry, with exception of SLCMJ height, which increased after the second match. The handgrip strength decreased throughout the matches, but similarly in both hands. Finally, the direction of asymmetry showed consistency throughout the matches only for SLCMJ height

Molecular mechanics of coiled coils loaded in the shear geometry

Coiled coils are important nanomechanical building blocks in biological and biomimetic materials. A mechanistic molecular understanding of their structural response to mechanical load is essential for elucidating their role in tissues and for utilizing and tuning these building blocks in materials applications. Using a combination of single-molecule force spectroscopy (SMFS) and steered molecular dynamics (SMD) simulations, we have investigated the mechanics of synthetic heterodimeric coiled coils of different length (3-4 heptads) when loaded in shear geometry. Upon shearing, we observe an initial rise in the force, which is followed by a constant force plateau and ultimately strand separation. The force required for strand separation depends on the coiled coil length and the applied loading rate, suggesting that coiled coil shearing occurs out of equilibrium. This out-of-equilibrium behaviour is determined by a complex structural response which involves helix uncoiling, uncoiling-assisted sliding of the helices relative to each other in the direction of the applied force as well as uncoiling-assisted dissociation perpendicular to the force axis. These processes follow a hierarchy of timescales with helix uncoiling being faster than sliding and sliding being faster than dissociation. In SMFS experiments, strand separation is dominated by uncoiling-assisted dissociation and occurs at forces between 25-45 pN for the shortest 3-heptad coiled coil and between 35-50 pN for the longest 4-heptad coiled coil. These values are highly similar to the forces required for shearing apart short double-stranded DNA oligonucleotides, reinforcing the potential role of coiled coils as nanomechanical building blocks in applications where protein-based structures are desired

Dialectical Interrelation Between: Problematic Situation, Real Problem, Scientific Problem, Object and Field, in the Investigation Design: A Necessary Reflection

All research responds to the need of solutions to a problem that directly or indirectly affects society. The development of the same largely certifies and determines the constant search for solutions. The main objective of the present study was to arrive at a clear conceptualization, as complete as possible, of some the most important terms that come up during an investigation design: Problematic Situation, Real Problem, Scientific Problem, and Object and Field, given the visible shortcomings observed in pre- and post-graduate theses when the research work is being developed and defended. The methodology consisted of basically developing a reflection around these terms (the vision that different authors have in this regard was very helpful), as well as the presentation of varied examples contributed to see the meaning of these important concepts more clearly. The study shows in a scientifically grounded way the achievement of the above. The way in which the presentation of the different concepts was handled removes any possibility of mistakes. Keywords: methodology scientific investigation, problem, object, field. Resumen Toda investigación parte del apremio en dar una respuesta a la solución de un problema que afecta de una manera directa o indirecta a la Sociedad. En gran medida, el propio desarrollo de la misma compulsa y determina esa constante búsqueda de soluciones. El objetivo principal del presente estudio fue llegar a una conceptualización clara, y lo más acabada posible, de algunos de los más importantes términos que se manejan durante el diseño de una investigación: Situación Problémica, Problema Real, Problema Científico, Objeto y Campo, dada las visibles falencias que se observan en tesistas de pre y postgrado a la hora de desarrollar y defender sus trabajos de investigación. La metodología consistió, básicamente, en desarrollar una reflexión en torno a estos términos; para lo cual resultó de gran ayuda la visión que tienen diferentes autores al respecto; así como, la exposición de variados ejemplos contribuyó a ver más definidamente el significado de estos importantes conceptos. El estudio muestra de forma científicamente fundamentada el logro de lo anterior. La forma en que se maneja la presentación de los diferentes conceptos aleja toda posibilidad de equívocos. Palabras clave: metodología investigación científica, problema, objeto, campo

Combined method of flow-reduced dump load for frequency control of an autonomous micro-hydropower in AC microgrids

Nowadays, microgrids (MGs) play a crucial role in modern power systems due to possibility of integrating renewable energies into grid-connected or islanded power systems. The Load Frequency Control (LFC) is an issue of paramount importance to ensure MGs reliable and safe operation. Specifically, in AC MGs, primary frequency control of each energy source can be guaranteed in order to integrate other energy sources. This paper proposes a micro-hydro frequency control scheme, combining the control of a reduced dump load and the nozzle flow control of Pelton turbines operating in autonomous regime. Some works have reported the integration of dump load and flow control methods, but they did not reduce the dump load value and adjust the nozzle flow linearly to the power value demanded by users, causing the inefficient use of water. Simulation results were obtained in Matlab®/Simulink® using models obtained from previous research and proven by means of experimental studies. The simulation of the proposed scheme shows that the frequency control in this plant is done in correspondence with the Cuban NC62-04 norm of power energy quality. In addition, it is possible to increase energy efficiency by reducing the value of the resistive dump load by up to 7.5% in a case study. The validation result shows a 60% reduction of overshoot and settling time of frequency temporal behavior of the autonomous micro-hydro.Peer ReviewedPostprint (published version

Propuesta de un modelo de administración estratégica desde un enfoque de calidad mediante los lineamientos para la acreditación de programas de pregrado del CNA para el mejoramiento de los procesos del programa de ingeniería industrial de la Universidad del Magdalena

El objetivo general de la investigación es Proponer un modelo de administración estratégica que permita mejorar el programa de ingeniería industrial de la Universidad del Magdalena desde un enfoque de calidad mediante Los Lineamientos de Acreditación de Programas de Pregrado dados por el CNA. El programa de Ingeniería Industrial de la Universidad del Magdalena desde su creación en el año 2000 se ha presentado como una opción para responder a los requerimientos del Departamento; si bien es cierto que ha venido creciendo con el tiempo y consolidándose en el contexto regional, también lo es que existen muchos aspectos por mejorar. Con la finalidad de proponer un modelo de Administración Estratégica para el Programa de Ingeniería Industrial de la universidad del Magdalena que permita su mejoramiento de acuerdo a sus propias necesidades, y teniendo en cuenta las variables que ha definido el Ministerio de Educación a través del CNA en los lineamientos expuestos para la acreditación de Programas de Pregrado en el territorio Nacional se ha desarrollado este proyecto a lo largo de 2 años. Este trabajo de investigación pretende proponer estrategias para el mejoramiento del programa desde la visión de la comunidad universitaria, en especial de los estudiantes, teniendo en cuenta factores tanto internos como externos

A rare case of cerebral venous thrombosis and disseminated intravascular coagulation temporally associated to the covid-19 vaccine administration

Globally, at the time of writing (20 March 2021), 121.759.109 confirmed COVID-19 cases have been reported to the WHO, including 2.690.731 deaths. Globally, on 18 March 2021, a total of 364.184.603 vaccine doses have been administered. In Italy, 3.306.711 confirmed COVID-19 cases with 103.855 deaths have been reported to WHO. In Italy, on 9 March 2021, a total of 6.634.450 vaccine doses have been administered. On 15 March 2021, Italian Medicines Agency (AIFA) decided to temporarily suspend the use of the AstraZeneca COVID-19 vaccine throughout the country as a precaution, pending the rulings of the European Medicines Agency (EMA). This decision was taken in line with similar measures adopted by other European countries due to the death of vaccinated people. On 18 March 2021, EMA’s safety committee concluded its preliminary review about thromboembolic events in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting, confirming the benefits of the vaccine continue to outweigh the risk of side effects, however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e., low levels of blood platelets with or without bleeding, including rare cases of cerebral venous thrombosis (CVT). We report the case of a 54-year-old woman who developed disseminated intravascular coagulation (DIC) with multi-district thrombosis 12 days after the AstraZeneca COVID-19 vaccine administration. A brain computed tomography (CT) scan showed multiple subacute intra-axial hemorrhages in atypical locations, including the right frontal and the temporal lobes. A plain old balloon angioplasty (POBA) of the right coronary artery was performed, without stent implantation, with restoration of distal flow, but with persistence of extensive thrombosis of the vessel. A successive thorax angio-CT added the findings of multiple contrast filling defects with multi-vessel involvement: at the level of the left upper lobe segmental branches, of left interlobar artery, of the right middle lobe segmental branches and of the right interlobar artery. A brain magnetic resonance imaging (MRI) in the same day showed the presence of an acute basilar thrombosis associated with the superior sagittal sinus thrombosis. An abdomen angio-CT showed filling defects at the level of left portal branch and at the level of right suprahepatic vein. Bilaterally, it was adrenal hemorrhage and blood in the pelvis. An evaluation of coagulation factors did not show genetic alterations so as the nasopharyngeal swab ruled out a COVID-19 infection. The patient died after 5 days of hospitalization in intensive care

VIRTUAL DIVING IN THE UNDERWATER ARCHAEOLOGICAL SITE OF CALA MINNOLA

The paper presents the application of the technologies and methods defined in the VISAS project for the case study of the underwater archaeological site of Cala Minnola located in the island of Levanzo, in the archipelago of the Aegadian Islands (Sicily, Italy). The VISAS project (http://visas-project.eu) aims to improve the responsible and sustainable exploitation of the Underwater Cultural Heritage by means the development of new methods and technologies including an innovative virtual tour of the submerged archaeological sites. In particular, the paper describes the 3D reconstruction of the underwater archaeological site of Cala Minnola and focus on the development of the virtual scene for its visualization and exploitation. The virtual dive of the underwater archaeological site allows users to live a recreational and educational experience by receiving historical, archaeological and biological information about the submerged exhibits, the flora and fauna of the place