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All metazoans depend on O2 delivery and consumption by the mitochondrial oxidative phosphorylation (OXPHOS) system to produce energy. A decrease in O2 availability (hypoxia) leads to profound metabolic rewiring. In addition, OXPHOS uses O2 to produce reactive oxygen species (ROS) that can drive cell adaptations through redox signalling, but also trigger cell damage1–4, and both phenomena occur in hypoxia4–8. However, the precise mechanism by which acute hypoxia triggers mitochondrial ROS production is still unknown. Ca2+ is one of the best known examples of an ion acting as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential and collaborating in ion transport10. Here we show that Na+ acts as a second messenger regulating OXPHOS function and ROS production by modulating fluidity of the inner mitochondrial membrane (IMM). We found that a conformational shift in mitochondrial complex I during acute hypoxia11 drives the acidification of the matrix and solubilization of calcium phosphate precipitates. The concomitant increase in matrix free-Ca2+ activates the mitochondrial Na+/Ca2+ exchanger (NCLX), which imports Na+ into the matrix. Na+ interacts with phospholipids reducing IMM fluidity and mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III, generating a redox signal. Inhibition of mitochondrial Na+ import through NCLX is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ import into the mitochondrial matrix controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences in cellular metabolism., Unión Europea, Ministerio de Economía, Comercio y Empresa (España)/Fondo Europeo de Desarrollo Regional, Comunidad de Madrid, Centro de Excelencia Severo Ochoa, Unidad de Excelencia Maria de Maeztu, Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Químicas, TRUE, pub

En la actualidad existe un gran número de personas aficionadas a la acuariofilia, que es la afición a la cría de peces y organismos acuáticos en un acuario, bajo unas condiciones controladas. La mayor parte de estas personas, realizan un control diario de los parámetros que influyen en este ecosistema, tales como la calidad de ésta, la temperatura, el pH, el alimento, las horas de iluminación etc. Existen sistemas comerciales que controlan todos estos parámetros sin la necesidad de un control manual, sin embargo el problema de estos sistemas es su precio elevado. Además, los sistemas actuales no abarcan todas las necesidades del usuario, lo que te obliga a adquirir diferentes controladores especializados en un grupo de parámetros o funciones. Para solventar estos problemas, en este proyecto se va a estudiar las necesidades técnicas del controlador para crear un sistema completo y económico, capaz de mantener el acuario sin supervisión el mayor tiempo posible en unas condiciones óptimas., Currently there are a large number of people fond of aquarium hobby, which is the hobby of raising fish and aquatic organisms in an aquarium, under controlled conditions. Most of these people carry out a daily control of the parameters that influence this ecosystem, such as its quality, temperature, pH, food, lighting hours, etc. There are commercial systems that control all these parameters without the need for manual control, however the problem with these systems is their high price. Furthermore, current systems do not cover all user needs, forcing you to purchase different specialized controllers in a group of parameters or functions. To solve these problems, this project will study the technical needs of the controller to create a complete and economical system, capable of keeping the aquarium unattended as long as possible under optimal conditions.

All metazoans depend on the consumption of O2 by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O2 to produce reactive oxygen species that can drive cell adaptations1,2,3,4, a phenomenon that occurs in hypoxia4,5,6,7,8 and whose precise mechanism remains unknown. Ca2+ is the best known ion that acts as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential10. Here we show that Na+ acts as a second messenger that regulates OXPHOS function and the production of reactive oxygen species by modulating the fluidity of the inner mitochondrial membrane. A conformational shift in mitochondrial complex I during acute hypoxia11 drives acidification of the matrix and the release of free Ca2+ from calcium phosphate (CaP) precipitates. The concomitant activation of the mitochondrial Na+/Ca2+ exchanger promotes the import of Na+ into the matrix. Na+ interacts with phospholipids, reducing inner mitochondrial membrane fluidity and the mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III. The inhibition of Na+ import through the Na+/Ca2+ exchanger is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences for cellular metabolism.

Coenzyme Q10 (CoQ10) deficiency syndrome is a rare disease included in the family of mitochondrial diseases, which is a heterogeneous group of genetic disorders characterized by defective energy production. CoQ10 biosynthesis in humans requires at least 11 gene products acting in a multiprotein complex within mitochondria. The high-throughput screening (HTS) method based on the stabilization of the CoQ biosynthesis complex (Q-synthome) produced by the COQ8 gene overexpression is proven here to be a successful method for identifying new molecules from natural extracts that are able to bypass the CoQ6 deficiency in yeast mutant cells. The main features of the new approach are the combination of two yeast targets defective in genes with different functions on CoQ6 biosynthesis to secure the versatility of the molecule identified, the use of glycerol as a nonfermentable carbon source providing a wide growth window, and the stringent conditions required to mark an extract as positive. The application of this pilot approach to a representative subset of 1200 samples of the Library of Natural Products of Fundación MEDINA resulted in the finding of nine positive extracts. The fractionation of three of the nine extracts allowed the identification of five molecules; two of them are present in molecule databases of natural extracts and three are nondescribed molecules. The use of this screening method opens the possibility of discovering molecules with CoQ10-bypassing action useful as therapeutic agents to fight against mitochondrial diseases in human patients.

Background: curricular strategies are applied to achieve objectives related to knowledge and skills in graduate education. Objective: to evaluate the application of the methodology to implement the curricular strategy of research and computer science in the third year of Medicine. Method: an evaluation research was carried out in the Faculty of Medical Sciences of the University of Medical Sciences of Holguín, between March-July 2017; Theoretical methods were applied: analysis-synthesis, induction-deduction and historical-logical; empirical: the documentary review, the observation to classes and the questionnaire survey to students and professors; and statistical procedures: the calculation of the relative and position indices, the scale element correlation and the Cronbach's Alpha. Results: three variables were determined to meet the research objective: knowledge of the methodology to implement the curricular research and information strategy in its theoretical and practical dimension, which was assessed as partially fulfilled; teacher preparation, where it was proven that they are oriented on how to apply their actions; and preparation of the students, partially fulfilled because they were assigned low values in some of their items, and after triangulating this information with the results of the observation to classes, some insufficiencies in its application were determined. Conclusions: the study carried out of the data obtained with the application of statistical methods and procedures made it possible to assess that the application of the methodology was partially fulfilled during the period analyzed., Fundamento: las estrategias curriculares se aplican para alcanzar objetivos relacionados con conocimientos y habilidades en la formación del egresado.Objetivo: valorar la aplicación de la metodología para implementar la estrategia curricular de investigación e informática en tercer año de Medicina.Método: se realizó una investigación de evaluación en la Facultad de Ciencias Médicas de la Universidad de Ciencias Médicas de Holguín, entre marzo-julio de 2017; se aplicaron métodos teóricos: análisis-síntesis, inducción-deducción e histórico-lógico; empíricos: la revisión documental, la observación a clases y la encuesta en forma de cuestionario a estudiantes y profesores; y procedimientos estadísticos: el cálculo de los índices relativo y de posición, la correlación elemento escala y el Alfa de Cronbach.Resultados: se determinaron tres variables para cumplir el objetivo de la investigación: conocimiento de la metodología para implementar la estrategia curricular de investigación e informática en su dimensión teórica y práctica, la cual fue valorada como parcialmente cumplida; preparación de los profesores, donde se comprobó que están orientados en cómo aplicar sus acciones; y preparación de los estudiantes, cumplida parcialmente pues fueron asignados valores bajos en algunos de sus ítems, y luego de triangulada esta información con los resultados de la observación a clases, se determinaron algunas insuficiencias en su aplicación.Conclusiones: el estudio realizado de los datos obtenidos con la aplicación de los métodos y procedimientos estadísticos permitió valorar que la aplicación de la metodología se cumplió de forma parcial durante el período analizado.

[EN] The kNN algorithm has three main advantages that make it appealing to the community: it is easy to understand, it regularly offers competitive performance and its structure can be easily tuning to adapting to the needs of researchers to achieve better results. One of the variations is weighting the instances based on their distance. In this paper we propose a weighting based on the Newton's gravitational force, so that a mass (or relevance) has to be assigned to each instance. We evaluated this idea in the kNN context over 13 benchmark data sets used for binary and multi-class classification experiments. Results in F1 score, statistically validated, suggest that our proposal outperforms the original version of kNN and is statistically competitive with the distance weighted kNN version as well.