Desarrollo de videojuego con Unity y Reinforcement Learning: TRON

[ES] En este trabajo se desarrolla un videojuego inspirado en la película de ciencia ficción TRON en el que se han empleado varias tecnologías diferentes que son habituales en la industria del videojuego como Unity y Blender; y además se explora la idea de emplear machine learning en vez de las técnicas usuales para crear las inteligencias artificiales que emplea un juego y el proceso a seguir para entrenarlas

¿Qué piensa el alumno del Grado en Educación Infantil sobre su competencia matemática?

RESUMEN: El presente estudio muestra lo que piensan los estudiantes que han finalizado el grado de Magisterio de Educación Infantil sobre su formación y competencia matemática. Para realizar este estudio se recogió, por medio de entrevistas semi-estructuradas, información de una muestra de x sujetos egresados de una universidad del norte de España. Se analizaron factores que influyen su formación matemática a lo largo de su vida académica. Los resultados muestran que los sujetos creen tener importantes carencias en su formación matemática, así como una falta de confianza en la formación recibida.ABSTRACT: This document shows a study on the training and mathematical competence of students who have completed the Early Childhood Education degree in a university in the north of Spain. To do this I have collected information through semi-structured interviews and analysed the results of the selected sample, evaluating the factors that influence the formation of these: gaps in the educational basis, the students’ attitude and the teacher’s influence.Grado en Magisterio en Educación Infanti

MALL, a membrane-tetra-spanning proteolipid overexpressed in cancer, is present in membraneless nuclear biomolecular condensates

Proteolipids are proteins with unusual lipid-like properties. It has long been established that PLP and plasmolipin, which are two unrelated membrane-tetra-spanning myelin proteolipids, can be converted in vitro into a water-soluble form with a distinct conformation, raising the question of whether these, or other similar proteolipids, can adopt two different conformations in the cell to adapt their structure to distinct environments. Here, we show that MALL, another proteolipid with a membrane-tetra-spanning structure, distributes in membranes outside the nucleus and, within the nucleus, in membrane-less, liquid-like PML body biomolecular condensates. Detection of MALL in one or other environment was strictly dependent on the method of cell fixation used, suggesting that MALL adopts different conformations depending on its physical environment —lipidic or aqueous— in the cell. The acquisition of the condensate-compatible conformation requires PML expression. Excess MALL perturbed the distribution of the inner nuclear membrane proteins emerin and LAP2β, and that of the DNA-binding protein BAF, leading to the formation of aberrant nuclei. This effect, which is consistent with studies identifying overexpressed MALL as an unfavorable prognostic factor in cancer, could contribute to cell malignancy. Our study establishes a link between proteolipids, membranes and biomolecular condensates, with potential biomedical implication

Solar-Simulated Ultraviolet Radiation Induces Abnormal Maturation and Defective Chemotaxis of Dendritic Cells

Exposure to ultraviolet (UV) light induces immunosuppression. Different evidences indicate that this phenomenon is mainly a consequence of the effect of UV light on skin dendritic cells (DC). To investigate the cellular and molecular basis of this type of immunosuppression, we assessed in vitro the effect of solar-simulated UV radiation on the phenotypic and functional characteristics of human monocyte-derived DC and Langerhans-like DC. UV radiation induced a decreased expression of molecules involved in antigen capture as DC-SIGN and the mannose receptor. This effect was accompanied by a diminished endocytic capacity, an enhanced expression of molecules involved in antigen presentation such as major histocompatibility complex-II and CD86, and a significant increase in their capability to stimulate T cells. Furthermore, irradiated DC failed to acquire a full mature phenotype upon treatment with lipopolysaccharide. On the other hand, solar-simulated radiation induced the secretion of tumor necrosis factor-αand interleukin (IL)-10 by DC, but no IL-12. Interestingly, solar-simulated UV radiation also caused an altered migratory phenotype, with an increased expression of CXCR4, and a lack of induction of CCR7, thus correlating with a high chemotactic response to stromal cell-derived factor 1(SDF-1) (CXCL12), but not to secondary lymphoid tissue chemokine (SLC) (CCL21). These data indicate that solar-simulated UV radiation induces a defective maturation and an anomalous migratory phenotype of DC

Oxidized low-density lipoprotein receptor in lymphocytes prevents atherosclerosis and predicts subclinical disease

Background: Although the role of Th17 and regulatory T cells in the progression of atherosclerosis has been highlighted in recent years, their molecular mediators remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/regulatory T cell immunity, and atherosclerosis development in animal models and in patients with subclinical disease. Methods: Low-density lipoprotein receptor-deficient chimeric mice expressing or not expressing CD69 on either myeloid or lymphoid cells were subjected to a high fat diet. In vitro functional assays with human T cells were performed to decipher the mechanism of the observed phenotypes. Expression of CD69 and NR4A nuclear receptors was evaluated by reverse transcription-polymerase chain reaction in 305 male participants of the PESA study (Progression of Early Subclinical Atherosclerosis) with extensive (n=128) or focal (n=55) subclinical atherosclerosis and without disease (n=122). Results: After a high fat diet, mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/regulatory T cell ratio in blood. Oxidized low-density lipoprotein was shown to bind specifically and functionally to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% CI, 0.40-0.94; P=0.006) after adjustment for traditional risk factors, the expression of NR4A1, the level of oxidized low-density lipoprotein, and the counts of different leucocyte subsets. Conclusions: CD69 depletion from the lymphoid compartment promotes a Th17/regulatory T cell imbalance and exacerbates the development of atherosclerosis. CD69 binding to oxidized low-density lipoprotein on T cells induces the expression of anti-inflammatory transcription factors. Data from a cohort of the PESA study with subclinical atherosclerosis indicate that CD69 expression in PBLs inversely correlates with the presence of disease. The expression of CD69 remained an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors.Funding was provided by the Spanish Ministry of Economy and Competitiveness: Plan Nacional de Salud SAF2017-82886-R to Dr Sánchez-Madrid, SAF2015-64767-R to Dr Martínez-González; Instituto de Salud Carlos III (AES 2016): PI16/01956 to Dr Martin, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; European Research Council, ERC- 2011-AdG294340-GENTRIS to Dr Sánchez-Madrid; Proyecto Integrado de Excelencia PIE13/041 and Fundació La Marató TV3 (20152330 31); and Comunidad Autónoma de Madrid CAM (S2017/BMD-3671) to Drs Martin and Sánchez-Madrid. Dr Tsilingiri is cofunded by the European Union Marie Curie Program. M. Relaño is supported by a Contratos Predoctorales Severo Ochoa para la formación de doctores (BES-2015–072625) from the Spanish Ministry of Economy and Competitiveness. This research has been cofinanced by Fondo Europeo de Desarrollo Regional. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The PESA study is cofunded equally by the Pro CNIC Foundation and Banco Santander, Madrid, Spai

Informe del Comité Científico de la Agencia Española de Consumo, Seguridad Alimentaria y Nutrición (AECOSAN) sobre los riesgos microbiológicos asociados al consumo de determinados alimentos por niños de 0 a 3 años

Los niños menores de 3 años son especialmente susceptibles a las enfermedades transmitidas por los alimentos debido, entre otros factores, a la inmadurez de su sistema inmunitario. La incidencia de enfermedades transmitidas por alimentos en este grupo de edad es mucho mayor que en la población en general. Teniendo en cuenta el estricto control sanitario existente durante la etapa pediátrica, los lactantes y niños de corta edad constituyen un grupo de población sobre el que las medidas de prevención basadas en la comunicación del riesgo y la educación para la salud pueden ser muy eficaces. Así pues, con el objetivo de establecer unos principios sobre los que realizar actividades de gestión y comunicación del riesgo, el Comité Científico ha elaborado un informe en el que se presentan aquellos patógenos transmitidos por alimentos de especial riesgo para lactantes y niños de corta edad, analizando en cada caso los factores que afectan a su supervivencia y crecimiento, así como las medidas de prevención más eficaces, incidiendo en aquellas que pueden ser ejercidas por los consumidores. Se han diferenciado los principales riesgos microbiológicos para cada grupo de edad: lactantes (leche materna o preparados para lactantes), niños que consumen alimentos triturados y aquellos que tienen una alimentación completa. En el caso de la lactancia materna, se revisan las infecciones que la contraindican de forma absoluta (brucelosis, VIH, HTLV) o relativa. Respecto a los lactantes alimentados con preparados en polvo, se incide especialmente en el riesgo de infección por Salmonella y Cronobacter, debido a que existen claras pruebas de una relación causal entre su presencia en los preparados para lactantes y el desarrollo de enfermedad en éstos, y se presentan las principales medidas higiénicas a respetar en la preparación y manipulación de biberones. En el caso de los niños que tienen una alimentación triturada o completa, se destaca la necesidad de incluir en cualquier campaña de comunicación del riesgo instrucciones relativas a la manipulación higiénica de los alimentos en el hogar. Por último, se incluye una lista de alimentos cuyo consumo puede suponer un riesgo para este grupo de población

Report of the Scientific Committee of the Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) on the risk of Tribulus te- rrestris in food supplements

Tribulus terrestris L. es una planta de la familia Zygophyllaceae cuyo uso en complementos alimenticios está autorizado en varios países de la Unión Europea y que contiene de manera natural varias sustancias activas, entre las que destacan saponósidos esteroídicos, alcaloides b-carbolínicos, favonoides y lignanamidas. La toxicidad de Tribulus terrestris en animales ha sido ampliamente documentada a lo largo de su historia como planta medicinal y se describen efectos negativos a nivel neuronal, muscular, hepático y renal. Algunos países consideran que utilizar partes de la planta de Tribulus terrestris en la elaboración de complementos alimenticios no es seguro, por lo que impiden su comercialización y lo comunican al sistema de alertas europeo RASFF (Rapid Alert System for Food and Feed). El Comité Científico ha realizado una evaluación del riesgo a fin de determinar si el consumo de frutos, partes aéreas de la planta y sus extractos de Tribulus terrestris en complementos alimenticios es seguro y ha concluido que no hay disponibles datos toxicológicos suficientes que permitan evaluar la seguridad del uso de partes de la planta de Tribulus terrestris en complementos alimenticios. En cualquier caso, se considera que las cantidades máximas diarias de Tribulus terrestris en complementos alimenticios no deberían superar las dosis de uso farmacológico y que en los complementos debería constar la parte de la planta empleada, y si se trata de un extracto u otra forma de preparación, así como el contenido en saponósidos.Tribulus terrestris L. is a plant from the Zygophyllaceae family whose use in food supplements is authorised in various European Union countries. In its natural form, it contains various active substances, the most notable of which are steroidal saponins, b-Carboline alkaloids, flavonoids and lignanamides. Tribulus terrestris’ toxicity to animals has been widely documented throughout its history as a medicinal plant and it has been reported to have negative neuronal, muscular, hepatic and renal effects. Some countries consider using parts of the Tribulus terrestris plant to produce food supplements to be unsafe so they do not allow such supplements to be sold. This is reported through the European Rapid Alert System for Food and Feed (RASFF). The Scientific Committee has conducted a risk assessment with the aim of determining whether consuming fruit, plant shoots and their extracts from Tribulus terrestris in food supplements is safe, concluding that there is insufficient toxicological data to assess how safe using parts of the Tribulus terrestris plant in food supplements is. In any case, the maximum daily quantity of Tribulus terrestris in food supplements should not exceed the dose used for pharmacological purposes and the part of the plant used, whether it was extracted or prepared in some other way and its saponin content should all be made clear on the supplement itself

Fernblock, a Nutriceutical with Photoprotective Properties and Potential Preventive Agent for Skin Photoaging and Photoinduced Skin Cancers

Many phytochemicals are endowed with photoprotective properties, i.e., the capability to prevent the harmful effects of excessive exposure to ultraviolet (UV) light. These effects include photoaging and skin cancer, and immunosuppression. Photoprotection is endowed through two major modes of action: UV absorption or reflection/scattering; and tissue repair post-exposure. We and others have uncovered the photoprotective properties of an extract of the fern Polypodium leucotomos (commercial name Fernblock). Fernblock is an all-natural antioxidant extract, administered both topically (on the skin) or orally. It inhibits generation of reactive oxygen species (ROS) production induced by UV including superoxide anion. It also prevents damage to the DNA, inhibits UV-induced AP1 and NF-κB, and protects endogenous skin natural antioxidant systems, i.e., CAT, GSH, and GSSR. Its photoprotective effects at a cellular level include a marked decrease of UV-mediated cellular apoptosis and necrosis and a profound inhibition of extracellular matrix remodeling. These molecular and cellular effects translate into long-term inhibition of photoaging and carcinogenesis that, together with its lack of toxicity, postulate its use as a novel-generation photoprotective nutriceutical of phytochemical origin

Flotillins Interact with PSGL-1 in Neutrophils and, upon Stimulation, Rapidly Organize into Membrane Domains Subsequently Accumulating in the Uropod

BACKGROUND: Neutrophils polarize and migrate in response to chemokines. Different types of membrane microdomains (rafts) have been postulated to be present in rear and front of polarized leukocytes and disruption of rafts by cholesterol sequestration prevents leukocyte polarization. Reggie/flotillin-1 and -2 are two highly homologous proteins that are ubiquitously enriched in detergent resistant membranes and are thought to shape membrane microdomains by forming homo- and hetero-oligomers. It was the goal of this study to investigate dynamic membrane microdomain reorganization during neutrophil activation. METHODOLOGY/PRINCIPAL FINDINGS: We show now, using immunofluorescence staining and co-immunoprecipitation, that endogenous flotillin-1 and -2 colocalize and associate in resting spherical and polarized primary neutrophils. Flotillins redistribute very early after chemoattractant stimulation, and form distinct caps in more than 90% of the neutrophils. At later time points flotillins accumulate in the uropod of polarized cells. Chemotactic peptide-induced redistribution and capping of flotillins requires integrity and dynamics of the actin cytoskeleton, but does not involve Rho-kinase dependent signaling related to formation of the uropod. Both flotillin isoforms are involved in the formation of this membrane domain, as uropod location of exogenously expressed flotillins is dramatically enhanced by co-overexpression of tagged flotillin-1 and -2 in differentiated HL-60 cells as compared to cells expressing only one tagged isoform. Flotillin-1 and -2 associate with P-selectin glycoprotein ligand 1 (PSGL-1) in resting and in stimulated neutrophils as shown by colocalization and co-immunoprecipitation. Neutrophils isolated from PSGL-1-deficient mice exhibit flotillin caps to the same extent as cells isolated from wild type animals, implying that PSGL-1 is not required for the formation of the flotillin caps. Finally we show that stimulus-dependent redistribution of other uropod-located proteins, CD43 and ezrin/radixin/moesin, occurs much slower than that of flotillins and PSGL-1. CONCLUSIONS/SIGNIFICANCE: These results suggest that flotillin-rich actin-dependent membrane microdomains are importantly involved in neutrophil uropod formation and/or stabilization and organize uropod localization of PSGL-1

Report of the Scientific Committee of the Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) on the conditions of use of certain substances to be used in food supplements-4

Los complementos alimenticios son alimentos cuyo fin es complementar la dieta normal y que consisten en fuentes concentradas de nutrientes (vitaminas y minerales) o de otras sustancias que tienen un efecto nutricional o fisiológico, en forma simple o combinada. Los complementos se comercializan en forma dosificada, se entregan al consumidor final únicamente preenvasados. En ningún caso, deben sustituir al uso de medicamentos sin una supervisión médica adecuada. Sólo deben utilizarse para complementar la dieta y, de forma general, su uso no es necesario si se sigue una dieta variada y equilibrada, a la que no pueden reemplazar. En España los complementos alimenticios están regulados por el Real Decreto 1487/2009 que traspuso a la legislación española la Directiva 2002/46/CE relativa a la aproximación de las legislaciones de los estados miembros en materia de complementos alimenticios. Sin embargo, actualmente sólo está regulado el uso de vitaminas y minerales, por lo que se ha solicitado al Comité Científico que realice una valoración de la propuesta de autorización de la utilización de determinadas sustancias distintas de vitaminas y minerales en la fabricación de complementos alimenticios. Las sustancias propuestas por la Agencia Española de Consumo, Seguridad Alimentaria y Nutrición (AECOSAN) son: ácido L-aspártico, L-citrulina, glicina, L-prolina, L-serina, L-arginina-L-aspartato, L-lisina-L-aspartato, L-lisina-L-glutamato, N-acetil-L-cisteína, N-acetil-L-metionina, hidroximetilbu- tirato, ácido lipoico, Monascus purpureus, carbón activo y lactulosa. El Comité Científico ha valorado cada propuesta, analizando las características y fuentes de cada sustancia, así como la nutrición, metabolismo y seguridad y ha concluido, en cada caso, si la presentada por la AECOSAN era aceptable desde el punto de vista de su seguridad en su uso como complemento alimenticio. En ningún caso, la evaluación realizada supone un aval de la eficacia biológica de las sustancias y dosis valoradas. El Comité Científico indica que, en todo caso es necesario que las personas que estén sometidas a tratamientos con medicamentos consulten con su médico la oportunidad o conveniencia de consumir complementos alimenticios dada la posibilidad de que existan interferencias en algunos casos.Food supplements are foods, the purpose of which is to supplement the normal diet and which consist of concentrated nutrient sources (vitamins and minerals) or other substances with a nutritional or physiological effect, alone or in combination. The supplements are marketed in dosage form and are only supplied to the end consumer prepacked. In no event should they replace the use of medicines without suitable medical supervision. They should only be used to supplement the diet and, on the whole, their usage is not required if the individual has a varied and balanced diet, which cannot be replaced. In Spain, food supplements are regulated by Royal Decree 1487/2009, which transposed Directive 2002/46/EC on the approximation of the laws of the Member States relating to food supplements into Spanish law. However, only the use of vitamins and minerals is currently regulated. Therefore the Scientific Committee has been asked to make an assessment of the proposal to authorise certain substances other than vitamins and minerals in the manufacture of food supplements. The substances proposed by the Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) are food supplements, L-aspartic acid, L-citrulline, glycine, L-proline, L-serine, L-arginine-L-aspar- tate, L-lysine L-aspartate, L-lysine-L-glutamate, N-acetyl-L-cysteine, N-acetyl-L-methionine, hidro- xymethylbutyrate, lipoic acid, Monascus purpureus, activated carbon and lactulose. The Scientific Committee has assessed each proposal, analysing the characteristics and sources of each substance, and the nutrition, metabolism and safety and has concluded, in each case, whether that submitted by the AECOSAN is acceptable from a safety viewpoint for use as a food supplement. In no event is the assessment intended as a guarantee of the biological efficiency of the substances and doses assessed. The Scientific Committee states that, in any case individuals undergoing medical treatment must seek medical advice as to the suitability of taking food supplements, given the possibility of interactions in certain cases