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Ischemic stroke is a primary cause of morbidity and mortality worldwide. Beyond the approved thrombolytic therapies, there is no effective treatment to mitigate its progression. Drug repositioning combinational therapies are becoming promising approaches to identify new uses of existing drugs to synergically target multiple disease-response mechanisms underlying complex pathologies. Here, we used a systems biology-based approach based on artificial intelligence and pattern recognition tools to generate in silico mathematical models mimicking the ischemic stroke pathology. Combinational treatments were acquired by screening these models with more than 5 million two-by-two combinations of drugs. A drug combination (CA) formed by ceruletide and alpha-1 antitrypsin showing a predicted value of neuroprotection of 92% was evaluated for their synergic neuroprotective effects in a mouse pre-clinical stroke model. The administration of both drugs in combination was safe and effective in reducing by 39.42% the infarct volume 24 h after cerebral ischemia. This neuroprotection was not observed when drugs were given individually. Importantly, potential incompatibilities of the drug combination with tPA thrombolysis were discarded in vitro and in vivo by using a mouse thromboembolic stroke model with t-PA-induced reperfusion, revealing an improvement in the forepaw strength 72 h after stroke in CA-treated mice. Finally, we identified the predicted mechanisms of action of ceruletide and alpha-1 antitrypsin and we demonstrated that CA modulates EGFR and ANGPT-1 levels in circulation within the acute phase after stroke. In conclusion, we have identified a promising combinational treatment with neuroprotective effects for the treatment of ischemic stroke.

Numerous studies suggest that the increased activity of p38MAPK plays an important role in the abnormal immune and inflammatory response observed in the course of neurodegenerative diseases such as Alzheimer's disease. On the other hand, High levels of p38MAPK are present in the brain during normal aging, suggesting the existence of mechanisms that keep the p38MAPK-regulated pro-inflammatory activity within physiological limits. In this study, we show that high p38MAPK activity in the hippocampus of old mice is in part due to the reduction in membrane cholesterol that constitutively occurs in the aging brain. Mechanistically, membrane cholesterol reduction increases p38MAPK activity through the stimulation of a subset of tyrosine kinase receptors (RTKs). In turn, activated p38MAPK increases the expression and activity of the phosphatase DUSP2, which is known to reduce the activity of different MAPKs, including p38MAPK. These results suggest that the loss of membrane cholesterol that constitutively occurs with age takes part in a negative-feedback loop that keeps p38MAPK activity levels within physiological range. Thus, conditions that increase p38MAPK activity such as cellular stressors or that inhibit DUSP2 will amplify inflammatory activity with its consequent deleterious functional changes.

Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

[ES] El ganado caprino español de producción lechera posee, en general, unas características notables en cuanto a su comportamiento productivo, características que pasan por unas elevadas producciones lecheras (400-600 kg de leche por lactación) con un solo ordeño al día. Sin embargo, actualmente, se ha detectado un problema en el proceso productivo global de la explotación, que es el del nulo interés económico de la cría de los cabritos para su posterior salida al mercado. Este problema se centra en que, dado que las características genéticas de los cabritos están dirigidas a la producción de leche, su crecimiento posee unos índices de conversión (kgs de pienso o leche necesarios para producir un incremento de 1 kg de peso vivo) muy elevados, lo que conduce a unos costes de producción que no son compensados por los precios de venta, reduciendo, así, la viabilidad económica de la explotación. En el caso de la raza Murciano-Granadina (MG), es la de mayor censo entre las razas caprinas españolas de aptitud láctea, y sus cabritos se comercializan entre 7 y 9 kg de peso vivo, con bajas velocidades de crecimiento (100-140 g/d). Para ayudar a mantener, o incluso elevar los rendimientos productivos de estas explotaciones lecheras, se pretende cruzar las hembras del rebaño, cuya prole no va a formar parte de la reposición, con una raza especializada en la producción de carne. A nivel global, suele ser la raza Boer la que se emplea en esta situación, y se cuenta con que este tipo de estrategias ya da, hoy en día, buenos resultados en las explotaciones de vacuno lechero. De entre todas las razas caprinas especializadas en la producción de carne, la raza Boer (BO) está considerada como una de las mejores razas de aptitud cárnica a nivel mundial, con velocidades de crecimiento en el período pre-destete propias del ovino (entre 208 y 291 g/d en lactancia natural). De hecho, se considera que el verdadero potencial de esta raza radica en que sus sementales sean utilizados en cruza, [EN] The Spanish goat milk production has, in general, remarkable characteristics as regards its productive behavior, characteristics that pass through high milk yields (400-600 kg of milk per lactation) with a single milking a day. However, at present, a problem has been detected in the overall productive process of the farm, which is the null economic interest of the rearing of the kids for their subsequent release to the market. This problem is centered on the fact that, given that the genetic characteristics of the goats are directed to milk production, their growth has conversion rates (kg of feed or milk needed to produce a 1 kg increase in live weight) , Which leads to production costs that are not offset by sales prices, thus reducing the economic viability of the farm. In the case of the Murciano-Granadina (MG) breed, it is the largest census among the Spanish caprine breeds of lactating ability, and their kids are traded between 7 and 9 kg live weight, with low growth rates (100-140 G / d). In order to help maintain or even increase the yields of these dairy farms, it is intended to cross the females of the herd, whose offspring will not be part of the replenishment, with a breed specialized in meat production. At the global level, it is usually the Boer breed that is used in this situation, and it is said that this type of strategies already gives good results today in dairy farms. Among all the goat breeds specializing in meat production, the Boer breed (BO) is considered one of the best breeds of meat aptitude worldwide, with growth rates in the pre-weaning period of the sheep (between 208 And 291 g / d in breastfeeding). In fact, it is considered that the true potential of this race lies in that their stallions are used in terminal crossbreedings with other breeds In order to arrive at valid conclusions about this approach, it is necessary to carry out an intense survey of the behavior of the animals of these crosses in different situations (artificial

[EN] This paper shows the teaching experience applied to the laboratory sessions of the subject of Science and Technology of Materials that is taught in the second year of the degrees of Electrical Engineering, Mechanical Engineering and Industrial Technologies Engineering in the Universitat Jaume I. The purpose of this experience is to facilitate the learning of the basic theoretical knowledge related to laboratory practice to develop and to make the students aware of the importance of preparing the practice prior to its development. This has been done by developing and using means or transmission formats of the contents to know before the practice which are more attractive and visual than the existing practice script, [ES] En este trabajo se muestra la experiencia docente aplicada a las sesiones de laboratorio de la asignatura de Ciencia y Tecnología de Materiales que se imparte en segundo curso de los grados de Ingeniería Eléctrica, Mecánica y en Tecnologías Industriales en la Universitat Jaume I. El propósito de esta experiencia es facilitar el aprendizaje de los conocimientos teóricos básicos relacionados con la práctica de laboratorio a desarrollar y sensibilizar a los alumnos sobre la importancia de preparar la práctica previamente a su desarrollo. Esto se ha realizado mediante el desarrollo y uso de medios o formatos de trasmisión de los contenidos a conocer previamente a la práctica que sean más atractivos y visuales que el guion de prácticas existente actualmente.

Mireia Coma,1 Raquel Valls,1 José Manuel Mas,1 Albert Pujol,1 Miquel Angel Herranz,2 Vicente Alonso,2,3 Jordi Naval21Anaxomics Biotech, Barcelona, Spain; 2Genocosmetics Laboratory, Barcelona, Spain; 3Unidad de Dermatología del Hospital Nisa 9 Octubre de Valencia, Valencia, SpainBackground: Perceived age has been defined as the age that a person is visually estimated to be on the basis of physical appearance. In a society where a youthful appearance are an object of desire for consumers, and a source of commercial profit for cosmetic companies, this concept has a prominent role. In addition, perceived age is also an indicator of overall health status in elderly people, since old-looking people tend to show higher rates of morbidity and mortality. However, there is a lack of objective methods for quantifying perceived age.Methods: In order to satisfy the need of objective approaches for estimating perceived age, a novel algorithm was created. The novel algorithm uses supervised mathematical learning techniques and error retropropagation for the creation of an artificial neural network able to learn biophysical and clinically assessed parameters of subjects. The algorithm provides a consistent estimation of an individual's perceived age, taking into account a defined set of facial skin phenotypic traits, such as wrinkles and roughness, number of wrinkles, depth of wrinkles, and pigmentation. A nonintervention, epidemiological cross-sectional study of cases and controls was conducted in 120 female volunteers for the diagnosis of perceived age using this novel algorithm. Data collection was performed by clinical assessment of an expert panel and biophysical assessment using the ANTERA 3D® device.Results and discussion: Employing phenotype data as variables and expert assignments as objective data, the algorithm was found to correctly classify the samples with an accuracy of 92.04%. Therefore, we have developed a method for determinin