992 resultados para Receptor 1 de la 5-hidroxitriptamina
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Sign.: [1]-4(4), 5(2)
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RESUMEN Su objetivo esencial: Regular el proceso de la edificación, está basado en 3 grandes pilares: 1.- Completar la configuración legal de los agentes que intervienen en el mismo, fijando sus obligaciones para así establecer las responsabilidades. 2.- Fomentar la calidad de los edificios. 3.- Fijar las garantías a los usuarios frente a los posibles daños. Estos tres fundamentos están intensamente relacionados, ya que, las obligaciones y responsabilidades de los agentes son la base de la constitución de las garantías a los usuarios, definidas mediante los requisitos básicos que deben satisfacer los edificios. Partiendo del análisis cualitativo y cuantitativo del grado de cumplimiento del objetivo de la nueva Ley, elaborado a través del estudio de sus tres pilares fundamentales, proponemos medidas tendentes a la plena entrada en vigor de la misma. Para ello se deberá desarrollar el Real Decreto previsto en la Disposición Adicional 2ª, una vez conseguido el grado de madurez de los sectores de la edificación y del seguro. En todo este proceso de estudio hemos podido apreciar que la objetiva identificación de los daños y en especial los que afectan la estabilidad del edificio, constituye una herramienta fundamental para la correcta atribución de responsabilidades a los agentes, basada en la aplicación de los tres grados de responsabilidad “ex lege” por daños materiales y sus plazos de prescripción surgidos del nuevo régimen impuesto por el art. 17 LOE Para avalar esta propuesta hemos analizado: 1.- El entorno económico, general y pormenorizado al sector de la edificación, en Europa y España durante el período comprendido entre los años 1990 y 2013, años previos y posteriores a la entrada en vigor de la Ley, dada la influencia de los ciclos de actividad producidos en la regulación del sector, las responsabilidades atribuidas a los agentes, el fomento de la calidad y las garantías ofrecidas a los adquirentes. 2.- Las diversas legislaciones sobre responsabilidades y garantías de los agentes de la edificación en los países de nuestro entorno económico. 3.- La gestación de la LOE, incidiendo en la evolución de los últimos borradores y su tramitación parlamentaria. 4.- El desarrollo doctrinal de la Transición desde el régimen de responsabilidades, fijado por el art. 1591 de Código Civil, y su Jurisprudencia, hacia el nuevo régimen de responsabilidades establecido por el art. 17 LOE. En esta tarea además de apreciar la asimilación, por parte de los Jueces y Magistrados, de los principios doctrinales de la LOE, hemos observado la labor de los peritos, de cuya experta identificación de las causas de los daños depende la justa y eficaz atribución de responsabilidades. 5 -. El grado de eficacia de la LOE a la vista de la estadística siniestral, de la que ya hay datos consolidados, tras la cancelación de casi 15.000 expedientes de reclamación a Arquitectos. 6 -. También hemos estudiado el grado de cumplimiento con el usuario y propietario de las garantías previstas en el art. 19 de la Ley y en la D.A. 1ª, los efectos reales alcanzados y las tareas pendientes por delante. Analizando la atribución de responsabilidades a los agentes de la edificación, dentro del primer pilar fundamental de la LOE, hemos estudiado las actuaciones de los peritos expertos y su incidencia en este objetivo, previa selección de casos de gran interés y dificultad. Fruto de ello se han formulado propuestas tendentes a la especialización de este colectivo, evitando conductas “irregulares” que tanto daño provocan a los agentes reclamados como a los propietarios afectados. Este daño es evidente pudiendo ocasionar condenas injustas, enriquecimientos ilícitos o bien falsas expectativas de satisfacción de daños mal dictaminados y costosas e ineficaces reparaciones. De cara a la consecución del pilar de la calidad de la edificación, mediante los requisitos básicos planteados por la LOE y desarrollados por el Código Técnico de la Edificación (Real Decreto 314/2006, de 17 de marzo), hemos procesado datos de expedientes de reclamaciones por daños que afectan a edificios ejecutados bajo el nuevo régimen LOE. Con esta base se han analizado las causas generadoras de las diversas lesiones y su frecuencia para que de este análisis puedan establecerse pautas de actuación para su prevención. Finalmente, tras demostrar que las garantías obligatorias impuestas por la LOE sólo abarcan un pequeño porcentaje de los posibles daños a la edificación, insistimos en la necesidad de la plena eficacia de la Ley mediante la aprobación de todas las garantías previstas y para todo tipo de edificaciones. En suma, se ha diseñado la tesis como una matriz abierta en la que podremos continuar incorporando datos de la evolución de la doctrina, la jurisprudencia y la estadística de los daños en la edificación. ABSTRACT The approval of Law 38/1999 on November 5, 1999, (Official Gazette BOE 266/1999 of 11.6.1999, p. 38925), was the culmination of a long period of over 20 years of gestation for which deep agreements were needed between all stakeholders affected. Although several parliamentary groups denounced its incomplete approval, regarding mandatory guarantees to the purchaser, its enactment caused general satisfaction among most of the the building agents. This assessment remains after fourteen years since its partial enactment. Its essential purpose, “to regulate the building process”, is based on 3 pillars: 1.- To complete the legal configuration of the agents involved in it, setting their obligations in order to establish their responsibilities. 2.- To promote the buildings quality. 3.- To specify users´guarantees against possible buildings damage. These three issues are strongly related, since the obligations and responsibilities of the actors are the basis of the users’guarantees constitution, defined by the basic performance required by buildings. Based on the qualitative and quantitative analysis of the fulfillment of the new law’s objectives, made by monitoring the three pillars, we propose measures to the full enactment of this Directive, by the development of the Royal Decree, provided in its Second Additional Provision, once maturity in the sectors of the building and insurance is achieved. Throughout this process of study we have seen that the skill identification of damage, particularly those affecting the stability of the building, is an essential tool for the proper allocation of responsibilities of the new regime installed by the art. 17 LOE, based on the application of the three degrees of responsibility "ex lege" for property damage and limitation periods. To support this proposal, we have analyzed: 1.- The evolution of the building sector in Europe and Spain during the years before and after the enactment of the Law, due to the influence of cycles of activity produced in industry regulation, the responsibilities attributed to agents, promotion of the quality and the assurances given to acquirers. 2.- The scope of various laws on liability and building agents warranties in the countries of our economic environment. 3.- The long period of LOE generation, focusing on the developments in recent drafts and parliamentary procedure. 4.- The doctrinal development in the Transition from the regime of responsibilities, set by art. 1591 of the Civil Code, and its Jurisprudence, to the new liability regime established by art. 17 LOE. In this task, while we have noted assimilation by the Judges and Magistrates of the doctrinal principles of the LOE, we have also analyzed the work of experts, whose skilled identification of the damage causes helps the fair and efficient allocation of responsibilities. 5 - The effectiveness of the LOE based on knowledge of the siniestral statistics, which are already consolidated data, after the cancellation of nearly 15,000 claims to Architects. 6.- We have also studied the degree of compliance with the user and owner guarantees, established in art. 19 and the D.A. 1th of the LOE, exposing the real effects achieved and the pending tasks ahead. Analyzing the allocation of the building agents´ responsibilities, within the first cornerstone of the LOE, we have studied the expert witnesses actions and their impact on this duty, selecting cases of great interest and difficulty in this aim. The result of this enterprise has been to propose the specialization of this group, avoiding "irregular" behaviors that create as much damage as the agents claimed to affected owners. This damage is evident and can cause wrong convictions, illicit enrichment, false expectations and inefficient and costly damage repairs. In order to achieve the pillar of building quality through the basic requirements set by the LOE and developed by the Technical Building Code (Royal Decree 314/ 2006 of 17 March), we have analyzed records of damage claims involving buildings executed under the new regime LOE. On this basis we have analyzed the root causes of various damages and their frequency, from these data it will be easy to propose lines of action for prevention. Finally, after demonstrating that mandatory warranties imposed by LOE cover only a small percentage of the potential building damage, we emphasize the need for the full effectiveness of the Law by the obligation all the guarantees provided in the art. 19 LOE, and for all types of buildings. In conclusion, this thesis is designed as an open matrix in which we will continue including data on the evolution of the doctrine, jurisprudence and the statistics of the damage to the building.
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Número 261 en el catálogo de Vicente Galbis e Hilari García. Título de la carpeta "A la libertad"
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Número 244 en el catálogo de Vicente Galbis e Hilari García
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El principal objetivo de esta tesis fue incrementar la eficiencia proteica en las dietas de rumiantes mediante el uso de proteínas protegidas (harina de girasol y guisante de primavera), así como mejorar la predicción de los aportes de proteína microbiana. Una partida de harinas comerciales de girasol (HG) y de guisante de primavera (GP) fueron tratadas con soluciones 4 N de ácido málico (268,2 g/L) o ácido ortofosfórico (130,6 g/L). Para cada harina, ácido y día de tratamiento, dos fracciones de 12,5 kg fueron pulverizadas sucesivamente en una hormigonera con la solución de ácido correspondiente mediante un pulverizador de campo. Las dos fracciones fueron mezcladas posteriormente y se dejaron reposar durante 1 h a temperatura ambiente. La mezcla fue luego secada en una estufa de aire forzado a 120 ºC durante 1 h. La estufa fue apagada inmediatamente después y el material tratado se mantuvo dentro de ésta hasta la mañana siguiente. El material fue removido durante el proceso de secado cada 30 min durante las primeras 2 h y cada 60 min durante las 5 h posteriores. Este proceso se repitió hasta conseguir las cantidades de harinas tratadas necesarias en los distintos ensayos. En el primer experimento (capitulo 3) se llevaron a cabo estudios de digestión ruminal e intestinal para evaluar los efectos de la aplicación de las soluciones ácidas indicadas y calor a fin de proteger las proteínas de HG y GP contra la degradación ruminal. Estos estudios se realizaron con tres corderos canulados en el rumen y en el duodeno. El estudio de digestión ruminal fue realizado en tres periodos experimentales en los que los corderos fueron alimentados sucesivamente con tres dietas isoproteicas que incluían HG y GP, sin tratar o tratadas con ácidos málico u ortofosfórico. Cada periodo experimental de 21 días incluyó sucesivamente: 10 días de adaptación a las dietas, un estudio del tránsito ruminal de las partículas de HG y GP (días 11 a 14), y la incubación de las muestras de ambos alimentos en bolsas de nailon (días 15–21). Las harinas incubadas en cada periodo experimental correspondieron a las que fueron incluidas en las dietas. Las bacterias ruminales fueron marcadas desde el día 11 hasta el día 21 del periodo experimental mediante infusión intra-ruminal continua con una fuente de 15N. Tras finalizar las incubaciones in situ el día 21 el rumen fue vaciado en cada periodo para aislar las bacterias asociadas a la fase sólida y liquida del rumen. El estudio de digestión intestinal fue realizado veinte días después del final del estudio ruminal a fin de eliminar el enriquecimiento en 15N de la digesta. En este estudio se incubaron muestras compuestas obtenidas mediante la combinación de los diferentes residuos no degradados en el rumen de forma que fuesen representativas de la composición química de la fracción no degradada en el rumen (RU). En esta fase los corderos fueron alimentados con la dieta sin tratar para determinar la digestibilidad de las harinas tanto tratadas como sin tratar mediante la técnica de las bolsas móviles. Además, las proteínas contenidas en las harinas tratadas y sin tratar, así como en las muestras correspondientes a los residuos a 0 h, las muestras compuestas anteriormente indicadas y las muestras no digeridas intestinalmente fueron extraídas y sometidas a electroforesis para determinar el sitio de digestión de las diferentes fracciones proteicas. Las estimaciones de la RU y la digestibilidad intestinal de la materia seca, la materia orgánica (solamente para RU), la proteína bruta (PB) y el almidón (solamente en GP) fueron obtenidos considerando la contaminación microbiana y las tasas de conminución y salida de partículas. Las estimaciones de RU y de la digestibilidad intestinal disminuyeron en todas las fracciones evaluadas de ambos alimentos al corregir por la contaminación microbiana acaecida en el rumen. Todas las estimaciones de RU aumentaron con los tratamientos de protección, incrementándose también la digestibilidad intestinal de la materia seca en la HG. Los bajos valores de la digestibilidad de la proteína de GP tratado y sin tratar sugieren la presencia de algún factor antitripsico no termolábil es esta harina. Los tratamientos de protección incrementaron consistentemente la fracción de materia seca y PB digerida intestinalmente en los dos alimentos, mientras que la fracción de almidón en la muestra de GP solamente aumentó numéricamente (60,5% de media). Sin embargo, los tratamientos también redujeron la fermentación de la materia orgánica, lo cual podría disminuir la síntesis de proteína microbiana. Los estudios de electroforesis muestran la práctica desaparición de la albumina por la degradación ruminal en ambos alimentos, así como que los cambios en otras proteínas de la muestra RU fueron más pronunciados en GP que en HG. La composición de las bacterias asociadas con las fases de digesta ruminal sólida (BAS) y líquida (BAL) fue estudiada para revisar la precisión de un sistema de predicción previo que determinaba la infravaloración del aporte de nutrientes correspondiente a las BAS cuando de usa 15N como marcador y las BAL como referencia microbiana (capitulo 4). Al comparar con BAS, BAL mostraron menores contenidos en materia orgánica, polisacáridos de glucosa y lípidos totales y un mayor contenido en PB, así como un mayor enriquecimiento en 15N. Los datos obtenidos en el estudio actual se ajustan bien a la ecuación previa que predice el enriquecimiento en 15N de las BAS a partir del mismo valor en BAL. Esta nueva ecuación permite establecer que se produce una infravaloración de un 22% en el aporte de PB al animal a partir de las BAS sintetizadas si las BAL son usadas como muestras de referencia. Una segunda relación calculada utilizando los valores medios por dieta expuestos en numerosos trabajos encontrados en la literatura confirma la magnitud de este error. Esta infravaloración asociada al uso de BAL como referencia fue mayor para el aporte de glucosa (43,1%) y todavía mayor para el aporte de lípidos (59,9%), como consecuencia de los menores contenidos de ambas fracciones en BAL frente a SAB. Estos errores deberían ser considerados para obtener mayor precisión en la estimación del aporte de nutrientes microbianos y mejorar la nutrición de los rumiantes. En el experimento 2 se realizó un estudio de producción (capitulo 5) para evaluar los efectos del tratamiento de las harinas HG y GP con soluciones de ácido málico o ácido ortofosfórico sobre el crecimiento, el consumo de concentrado y el rendimiento y engrasamiento de las canales de corderos de engorde. Noventa corderos machos de cruce entrefino procedentes de tres granjas comerciales (peso inicial medio = 14,6, 15,3 y 13,3 kg, respectivamente) fueron asignados aleatoriamente a cinco dietas con diferentes niveles de proteína y diferentes tratamientos con ácidos y engordados hasta un peso medio al sacrificio de 25 kg. Las fuentes de proteína en el pienso control (C; PB=18,0%) fueron harina de soja, HG y GP sin tratar. En tres de los piensos experimentales, las harinas tratadas con ácido ortofosfórico sustituyeron a las de HG y GP sin tratar (Control Ortofosfórico, PC; PB=18,0% sobre materia seca), sustituyéndose, además, la harina de soja parcialmente (Sustitución Media Ortofosfórico, MSP; PB=16,7%) o totalmente (Sustitución Total Ortofosfórico, TSP; PB=15,6%). Finalmente, en uno de los piensos el ácido ortofosfórico fue reemplazo por acido málico para proteger ambas harinas (Sustitución Media Málico, MSM; PB= 16,7%). La paja de trigo (fuente de forraje) y el concentrado fueron ofrecidos ad libitum. Dieciocho corderos fueron distribuidos en seis cubículos con tres animales para cada dieta. Los datos fueron analizados según un análisis factorial considerando el peso inicial como covariable y la granja de procedencia como bloque. Los datos de consumo de concentrado y eficiencia de conversión fueron analizados usando el cubículo como unidad experimental, mientras que los datos sobre ganancia media diaria, rendimiento a la canal, grasa dorsal y grasa pélvico renal fueron analizados usando el cordero como unidad experimental. No se encontró ningún efecto asociado con el nivel de PB sobre ninguna variable estudiada. Esto sugiere que usando proteínas protegidas es posible utilizar concentrados con 15,6% de PB (sobre materia seca) disminuyendo así la cantidad de concentrados de proteína vegetal a incluir en los piensos y la calidad de los concentrados proteicos. Los corderos alimentados con la dieta MSM tuvieron mayores ganancias medias diarias (15,2%; P= 0,042), y mejores rendimiento a la canal en caliente (1,3 unidades porcentuales; P= 0,037) que los corderos alimentados con el concentrado MSP. Esto podría ser explicado por los efectos benéficos ruminales del malato o por el mayor efecto de protección conseguido con el ácido málico. ABSTRACT The main objective of this thesis project was to increase the protein efficiency in ruminant diets by using protected protein (sunflower meal and spring pea), and improving the prediction of microbial protein supply. Commercial sunflower meal (SFM) and spring pea (SP) were treated with 4 N solutions (200 mL/kg) of malic acid (268.2 g/L) or orthophosphoric acid (130.6 g/L). Daily, two fractions of 12.5 kg of one of these meals were successively sprayed with the tested acid solution in a concrete mixer using a sprayer. Both fractions were then mixed and allowed to rest for 1 h at room temperature. The blend was then dried in a forced air oven at 120 ºC for 1 h. Then the oven was turned off and the treated material was left in the oven overnight. During the drying process, the material was stirred every 30 min during the first 2 h and then every 60 min for the subsequent 5 h. This process was repeated until the amounts of treated flour needed for the different trials performed. In the first experiment (chapter 3), ruminal and intestinal digestion trials were conducted to study the effects of the application of these acid solutions and heat to protect proteins of SFM and SP against ruminal degradation using three wethers fitted with rumen and duodenum cannulae. The ruminal digestion study was carried out in three experimental periods in which the wethers were successively fed three isoproteic diets including SFM and SP, untreated or treated with malic or orthophosphoric acids. The experimental periods of 21 days included successively: 10 days of diet adaptation, SFM and SP particle ruminal transit study (days 11–14) and ruminal nylon-bag incubations (days 15–21). The meals incubated in each experimental period were those corresponding to the associated diet. Rumen bacteria were labelled from days 11 to 21 by continuous intra-ruminal infusion of a 15N source and the rumen was emptied at the end of in situ incubations in each period to isolate solid adherent bacteria and liquid associate bacteria. The intestinal digestion trial was conducted twenty days after the end of the ruminal studies to eliminate the 15N enrichment in the digesta. The tested samples were composite samples obtained pooling the different ruminally undegraded residues to be representative of the chemical composition of the ruminally undegraded fraction (RU). Wethers were fed the untreated diet to determine the intestinal digestibility of untreated and treated meals using the mobile nylon bag technique. In addition, protein in untreated and treated meals and their 0 h, composite and intestinally undigested samples were extracted and subjected to electrophoresis to determine the digestion site of the different protein fractions. Estimates of the RU and its intestinal digestibility of dry matter, organic matter (only for RU), crude protein (CP) and starch (only in SP) were obtained considering ruminal microbial contamination and particle comminution and outflow rates. When corrected for the microbial contamination taking place in the rumen, estimates of RU and intestinal digestibility decreased in all tested fractions for both feeds. All RU estimates increased with the protective treatments, whereas intestinal digestibility-dry matter also increased in SFM. Low intestinal digestibility-CP values in untreated and treated samples suggested the presence of non-heat labile antitrypsin factors in SP. Protective treatments of both feeds led to consistent increases in the intestinal digested fraction of dry matter and CP, being only numerically different for SP-starch (60.5% as average). However, treatments also reduced the organic matter fermentation, which may decrease ruminal microbial protein synthesis. Electrophoretic studies showed albumin disappearance in both SFM and SP, whereas changes in other RU proteins were more pronounced in SP than SFM. The chemical composition of bacteria associated with solid (SAB) and liquid (LAB) rumen-digesta phases was studied to examine the accuracy of a previous regression system determining the underevaluation of SAB-nutrient supply using 15N as marker and LAB as microbial reference (chapter 4). Compared with SAB, LAB showed lower contents of organic matter, polysaccharide-glucose and total lipids and the opposite for the CP content and the 15N enrichment. Present data fitted well to the previous relationship predicting the 15N enrichment of SAB from the same value in LAB. This new equation allows establishing an underevaluation in the supply of CP from the synthesized SAB in 22.0% if LAB is used as reference. Another relationship calculated using mean diet values from the literature confirmed the magnitude of this error. This underevaluation was higher for the supply of glucose (43.1%) and still higher for the lipid supply (59.9%) as a consequence of the lower contents of these both fractions in LAB than in SAB. These errors should be considered to obtain more accurate estimates of the microbial nutrient supply and to improve ruminant nutrition. A production study was performed in experiment 2 (chapter 5) to examine the effects of treating SFM and SP meals with orthophosphoric or malic acid solutions on growth performance, concentrate intake, and carcass yield and fatness of growing-fattening lambs. Ninety "Entrefino" cross male lambs from three commercial farms (average initial body weights (BW) = 14.6, 15.3 and 13.3 kg) were randomly assigned to five diets with different acid treatment and protein levels, and fattened to an average slaughter weight of 25 kg. Protein sources in the control concentrate (C; CP=18%) were soybean meal and untreated SFM and SP. In three of the experimental concentrates, orthophosphoric acid-treated meals substituted untreated SFM and SP (Orthophosphoric Control, PC; CP=18% dry matter basis), and soybean meal was partially (Medium Substitution Orthophosphoric, MSP; CP=16.7%) or totally removed (Total Substitution Orthophosphoric, TSP; CP=15.6%). In addition, in one concentrate orthophosphoric acid was replaced by malic acid to protect these meals (Medium Substitution Malic, MSM; CP= 16.7%). Wheat straw (roughage source) and concentrate were offered ad libitum. Eighteen lambs were allocated to six pens of three animals on each diet. Data were analyzed using a factorial analysis with initial body weight BW as covariate and farm of origin as block. Data on concentrate intake and feed conversion efficiency were analyzed using pen as experimental unit, while data on average daily gain, carcass yield, dorsal fat, and kidney-pelvic-fat were analyzed with lamb as experimental unit. No effect associated with the CP level was observed on any parameter. This suggests that with protected proteins it is possible to feed concentrates with 15.6% CP (dry matter basis) reducing the quantity of vegetable protein meals to include in the concentrate as well as the quality of the protein concentrates. Lambs feed MSM had higher average daily gains (15.2%; P= 0.042), and better hot carcass yields (1.3 percentage points; P= 0.037) than lambs feed MSP. This probably can be explained by ruminal malate actions and by greater protection effects obtained with malic acid.
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El propósito de este estudio fue la construcción y validación de un instrumento de medición de barreras a la práctica de la actividad física y deportiva por parte de las personas adultas desde la teoría ecológico social y analizar la presencia de las diferentes barreras así como las innovaciones y alternativas de conciliación a las barreras relacionadas con el empleo, el cuidado de hijos e hijas y las tareas del hogar, identificando las posibles diferencias existentes en función del género y del tipo de demanda en la población adulta de la Comunidad de Madrid. Se ha realizado un estudio cuantitativo, descriptivo y transversal en una muestra representativa de la población residente en la Comunidad de Madrid entre 30 y 64 años. El tipo de muestreo fue probabilístico, de tipo polietápico según tamaño demográfico de municipio y género, con un margen de error del ± 5,27% y un intervalo de confianza del 95,5%. El tamaño de la muestra final fue de 360 personas (50,3% mujeres, 49,7% hombres), quienes completaron un cuestionario estructurado mediante entrevista personal cara a cara en su domicilio entre octubre y diciembre de 2011, que incluía una escala de barreras específica, así como sub-cuestionarios de innovaciones y alternativas de conciliación vinculados a los tres ítems relacionados con el empleo, cuidado de hijos e hijas y hogar de la escala de barreras. La escala de barreras fue completada por las personas practicantes de actividad física y deportiva que deseaban realizar otra actividad, es decir, por la Demanda Establecida, así como por las personas no practicantes pero deseosas de hacerlo o Demanda Latente, y las personas no practicantes no interesadas en practicar o Demanda Ausente (n=246). Las personas que alcanzaron elevadas puntuaciones en los tres ítems de la escala de barreras vinculados al empleo, cuidado de hijos e hijas y hogar, completaron sub-cuestionarios específicos de innovaciones y alternativas de conciliación vinculados a estas barreras. Para el estudio métrico de los ítems y la dimesionalidad de la escala de barreras se llevaron a cabo análisis descriptivos de los ítems, análisis correlacionales y análisis factoriales exploratorios (AFE). Como resultado se obtuvo una escala de barreras constituida por 13 ítems que explicaron el 59,1% de la variabilidad total de los datos, agrupados en cuatro dimensiones denominadas: Barreras Interpersonales (2 ítems), Barreras Individuales (4 ítems), Barreras Comunidad-Institucionales (4 ítems) y Barreras Obligaciones-Tiempo (3 ítems). Los datos de la escala de barreras y los sub-cuestionarios de innovaciones y alternativas de conciliación fueron analizados con el SPSS v. 18. Para la comparación de variables cuantitativas y ordinales se utilizaron ANOVAS de dos factores (género por tipo de demanda), el tamaño del efecto para esta prueba se cuantificó mediante eta cuadrado. Los resultados se expresaron como porcentajes para las variables nominales y como medias y desviaciones típicas para las variables ordinales y cuantitativas. El nivel de riesgo se fijó en 0,05. El instrumento presentó una fiabilidad aceptable (α=0,58) en consonancia con el modelo ecológico social presentando dimensiones que explicaron los niveles de influencia de las diferentes esferas. Los resultados obtenidos permitieron avalar tanto la adecuación de las propiedades psicométricas de los ítems, así como la validez y fiabilidad de la escala de barreras para la práctica de actividad física y deportiva. Los distintos análisis realizados han aportado evidencia de la validez de una estructura de cuatro dimensiones acorde a los planteamientos teóricos previos de los modelos ecológicos sociales. En la dimensión barreras Individuales se identificaron diferencias según el tipo de demanda (F2,237=40,28; p<0,001; η2=0,25) y el género (F1,237=8,72; p<0,01; η2=0,84). En la dimensión barreras Interpersonales se identificaron diferencias de género (F1,239 =14,9; p<0,01; η2=0,06) pero no entre demandas (F2,239=2,35; p>0,05; 1-β=0,47). En la dimensión Barreras Obligaciones-Tiempo se identificaron diferencias en función del tipo de demanda (F2,239=3,88; p<0,05; η2=0,03) sin presentar diferencias entre hombres y mujeres (F1,239=1,06; p>0,05; 1-β=0,18). Por último, en la dimensión Comunidad Institucionales, se identificaron diferencias en función del tipo de demanda (F2,240=5,69; p<0,01; η2=0,045) y no hubo diferencias en función del género (F1,240=0,65; p>0,05; 1-β=0,13). Las innovaciones y alternativas de conciliación relacionadas con el empleo más valoradas fueron la de flexibilidad en los horarios de trabajo y adecuación de horarios; las más valoradas relacionadas con la barrera cuidado de hijos fueron que en la instalación deportiva se ofertaran actividades físicas conjuntas, en las en las que pudiesen participar madres e hijos y que la instalación deportiva ofreciera, en el mismo horario, actividades para ellos y sus hijos, y, por último, las más valoradas en relación con las tareas del hogar, una mayor implicación de la pareja seguida por una mayor implicación de los hijos. ABSTRACT The objectives of this study were to build and validate an instrument to measure the barriers of adult people to the practice of sport and physical activities from the perspective of the social-ecological theory, analyse the presence of the different barriers, as well as the innovations and alternatives regarding conciliation with work and the care of children and home as barriers, identifying the possible differences that exist based on gender and the type of demand of the adult population within the Community of Madrid. For this, a quantitative, descriptive and transversal study was carried out on a representative sample of the resident population of the Community of Madrid, ages ranging from 30 to 64 years old. Given that is an infinite or very large population, and working with an interval of confidence of the 95,5%, and assuming in the population variance, the worst case of p equal to q, the margin of sampling error was ± 5,27. The sample consisted of 360 people (50,3% women, 49,7% men), who completed a questionnaire during face-to-face personal interviews between October and December 2011. The questionnaire included a scale of specific barriers, as well as sub-questionnaires on the innovations and alternatives linked to the three items regarding work, the care of children and home of the barriers scale. The barriers scale was completed by people who practice physical and sport activities and wanted to do other activities, i.e. by the Established Demand; by people who do not practice these activities but would like to do so, i.e. Latent Demand; and by people who do not practice these activities and have no desire to do so, i.e. Absent Demand (n=246). The people who peaked on the three items of the barriers scale regarding work, the care of children and home, then completed specific sub-questionnaires on the innovations and alternatives for conciliation related to these barriers. The metric study of the items and the dimensionality of the barriers scale was carried out through descriptive analyses of the items, as well as correlation analyses and exploratory factor analyses (EFA). This resulted in a barriers scale composed of 13 items that explained 59,1% of the total variability of the data, grouped in four dimensions as follows: Interpersonal Barriers (2 items), Individual Barriers (4 items), Community-Institutional Barriers (4 items) and Obligations-Time Barriers (3 items). The data obtained from the barriers scale and sub-questionnaires on the innovations and alternatives for conciliation were analyzed using software SPSS v. 18. Two-way ANOVA (gender by type of demand) was used for the comparison of quantitative and ordinal variables, and the effect size for this test was quantified with eta squared. The results were expressed as percentages for nominal variables, and as means and standard deviations for quantitative and ordinal variables. The level of risk was set at 0,05. The instrument showed an acceptable reliability (α=0,58) in line with the social-ecological model, providing dimensions that explained the influence levels of the different spheres. The results obtained establish both the adaptation of the psychometric properties of the items, and the validity and reliability of the barriers scale for the practice of physical and sport activities. The different analyses have supported the validity of a four-dimensional structure consistent with the previous theoretical approaches on the social-ecological models, while showing adequate statistical indices. The differences identified in the Individual Barriers dimension were based on the type of demand (F2,237=40,28; p<0,001; η2=0,25) and gender (F1,237=8,72; p<0,01; η2=0,84). The differences identified in the Interpersonal Barriers dimension were based on gender (F1,239 =14,9; p<0,01; η2=0,06) but not on demand (F2,239=2,35; p>0,05; 1-β=0,47). The differences identified for the Obligations-Time Barriers dimension were based on the type of demand (F2,239=3,88; p<0,05; η2=0,03) and did not show differences between men and women (F1,239=1,06; p>0,05; 1-β=0,18). Finally, the differences identified for the Community-Institutional Barriers dimension were based on the type of demand (F2,240=5,69; p<0,01; η2=0,045) and provided no differences based on gender (F1,240=0,65; p>,05; 1-β=0,13). The most valued innovations and alternatives for conciliation regarding work were the adaptation and flexibility of working hours and timetables; the most valued related to the care of children were the offer of joint activities for adults and children in sport centres, as well as separate activities within the same timetable; and, finally, the most valued regarding the home was a higher degree of participation and involvement on the part of the spouse or partner, followed by a higher degree of participation and involvement on the part of the children.
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[1]. Visitando una alquería, dos mujeres y un hombre con una paella, 1917 (1 par estereoscópico) (1 fot.) [2]. Jardín con flores en Valencia, 1917 (2 pares estereoscópicos) (1 fot.) [3-5]. En la huerta, en el jardín de una alquería un grupo de mujeres con tres niños, una joven con una maceta, una joven con botijo andando por un camino con marcas de ruedas (3 pares estereoscópicos) (3 fot.) [6]. Pareja de ancianos labradores en su barraca, 1917 (1 par estereoscópico) (1 fot.) [7-14]. Miembros del Centro Escolar y Mercantil fotografiados junto a los labradores en su barraca, en la huerta y en un jardín, 1917 (7 pares estereoscópicos) (8 fot.) [15]. Miembros del Centro Escolar y Mercantil en la terraza de una Ermita comiendo bocadillos, en una de las fotos el sacerdote, 1917 (1 par estereoscópico) (2 fot.)
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It is widely accepted that interleukin-1β (IL-1β), a cytokine produced not only by immune cells but also by glial cells and certain neurons influences brain functions during infectious and inflammatory processes. It is still unclear, however, whether IL-1 production is triggered under nonpathological conditions during activation of a discrete neuronal population and whether this production has functional implications. Here, we show in vivo and in vitro that IL-1β gene expression is substantially increased during long-term potentiation of synaptic transmission, a process considered to underlie certain forms of learning and memory. The increase in gene expression was long lasting, specific to potentiation, and could be prevented by blockade of potentiation with the N-methyl-d-aspartate (NMDA) receptor antagonist, (±)-2-amino-5-phosphonopentanoic acid (AP-5). Furthermore, blockade of IL-1 receptors by the specific interleukin-1 receptor antagonist (IL-1ra) resulted in a reversible impairment of long-term potentiation maintenance without affecting its induction. These results show for the first time that the production of biologically significant amounts of IL-1β in the brain can be induced by a sustained increase in the activity of a discrete population of neurons and suggest a physiological involvement of this cytokine in synaptic plasticity.
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Several G-protein coupled receptors, such as the β1-adrenergic receptor (β1-AR), contain polyproline motifs within their intracellular domains. Such motifs in other proteins are known to mediate protein–protein interactions such as with Src homology (SH)3 domains. Accordingly, we used the proline-rich third intracellular loop of the β1-AR either as a glutathione S-transferase fusion protein in biochemical “pull-down” assays or as bait in the yeast two-hybrid system to search for interacting proteins. Both approaches identified SH3p4/p8/p13 (also referred to as endophilin 1/2/3), a SH3 domain-containing protein family, as binding partners for the β1-AR. In vitro and in human embryonic kidney (HEK) 293 cells, SH3p4 specifically binds to the third intracellular loop of the β1-AR but not to that of the β2-AR. Moreover, this interaction is mediated by the C-terminal SH3 domain of SH3p4. Functionally, overexpression of SH3p4 promotes agonist-induced internalization and modestly decreases the Gs coupling efficacy of β1-ARs in HEK293 cells while having no effect on β2-ARs. Thus, our studies demonstrate a role of the SH3p4/p8/p13 protein family in β1-AR signaling and suggest that interaction between proline-rich motifs and SH3-containing proteins may represent a previously underappreciated aspect of G-protein coupled receptor signaling.
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Several scaffold proteins for neurotransmitter receptors have been identified as candidates for receptor targeting. However, the molecular mechanism underlying such receptor clustering and targeting to postsynaptic specializations remains unknown. PSD-Zip45 (also named Homer 1c/vesl-1L) consists of the NH2 terminus containing the enabled/VASP homology 1 domain and the COOH terminus containing the leucine zipper. Here, we demonstrate immunohistochemically that metabotropic glutamate receptor 1α (mGluR1α) and PSD-Zip45/Homer 1c are colocalized to synapses in the cerebellar molecular layer but not in the hippocampus. In cultured hippocampal neurons, PSD-Zip45/Homer1c and N-methyl-d-aspartate receptors are preferentially colocalized to dendritic spines. Cotransfection of mGluR1α or mGluR5 and PSD-Zip45/Homer 1c into COS-7 cells results in mGluR clustering induced by PSD-Zip45/Homer 1c. An in vitro multimerization assay shows that the extreme COOH-terminal leucine zipper is involved in self-multimerization of PSD-Zip45/Homer 1c. A clustering assay of mGluRs in COS-7 cells also reveals a critical role of this leucine-zipper motif of PSD-Zip45/Homer 1c in mGluR clustering. These results suggest that the leucine zipper of subsynaptic scaffold protein is a candidate motif involved in neurotransmitter receptor clustering at the central synapse.
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To determine the role of PTHrP in fetal calcium metabolism, blood calcium was measured in mice homozygous (HOM) for deletion of the PTHrP gene. On day 18.5 of gestation, ionized calcium and the maternal–fetal calcium gradient were significantly reduced in HOM PTHrP-ablated fetuses compared with that of their littermates. To assess the placental contribution to the effect of PTHrP, 45Ca and 51Cr-EDTA (as a blood diffusional marker) were administered by intracardiac injection to pregnant, heterozygous dams on day 17.5 of gestation. Five minutes after the injection, whole fetal 45Ca accumulation was significantly decreased in HOM PTHrP-ablated fetuses compared with that of their littermates. Next, two fetuses from each litter were injected in utero with fragments of PTHrP, PTH, or diluent 1 h before administering 45Ca and 51Cr to the dam. PTHrP-(1–86) and PTHrP-(67–86) significantly increased relative 45Ca accumulation in HOM PTHrP-ablated fetuses, but PTHrP(1–34), PTH-(1–84), and the diluent had no effect. Finally, similar studies were performed on fetal mice that lacked the PTH/PTHrP receptor gene. Ionized calcium was significantly reduced in HOM PTH/PTHrP receptor-ablated fetuses. However, 5 min after maternal injection of 45Ca and 51Cr, relative accumulation of 45Ca was significantly increased in these fetuses. It was concluded that PTHrP is an important regulator of fetal blood calcium and placental calcium transport. In addition, the bioactivity of PTHrP for placental calcium transport is specified by a mid-molecular region that does not use the PTH/PTHrP receptor.
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Using a consensus sequence in inositol phosphate kinase, we have identified and cloned a 44-kDa mammalian inositol phosphate kinase with broader catalytic capacities than any other member of the family and which we designate mammalian inositol phosphate multikinase (mIPMK). By phosphorylating inositol 4,5-bisphosphate, mIPMK provides an alternative biosynthesis for inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. mIPMK also can form the pyrophosphate disphosphoinositol tetrakisphosphate (PP-InsP4) from InsP5. Additionally, mIPMK forms InsP4 from Ins(1,4,5)P3 and InsP5 from Ins(1,3,4,5)P4.
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Protracted administration of diazepam elicits tolerance, whereas discontinuation of treatment results in signs of dependence. Tolerance to the anticonvulsant action of diazepam is present in an early phase (6, 24, and 36 h) but disappears in a late phase (72–96 h) of withdrawal. In contrast, signs of dependence such as decrease in open-arm entries on an elevated plus-maze and increased susceptibility to pentylenetetrazol-induced seizures were apparent 96 h (but not 12, 24, or 48 h) after diazepam withdrawal. During the first 72 h of withdrawal, tolerance is associated with changes in the expression of GABAA (γ-aminobutyric acid type A) receptor subunits (decrease in γ2 and α1; increase in α5) and with an increase of mRNA expression of the most abundant form of glutamic acid decarboxylase (GAD), GAD67. In contrast, dl-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR1 subunit mRNA and cognate protein, which are normal during the early phase of diazepam withdrawal, increase by approximately 30% in cortex and hippocampus in association with the appearance of signs of dependence 96 h after diazepam withdrawal. Immunohistochemical studies of GluR1 subunit expression with gold-immunolabeling technique reveal that the increase of GluR1 subunit protein is localized to layer V pyramidal neurons and their apical dendrites in the cortex, and to pyramidal neurons and in their dendritic fields in hippocampus. The results suggest an involvement of GABA-mediated processes in the development and maintenance of tolerance to diazepam, whereas excitatory amino acid-related processes (presumably via AMPA receptors) may be involved in the expression of signs of dependence after withdrawal.
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Peroxisome proliferators induce stearoyl-CoA desaturase activity (EC 1.14.99.5) in liver [Kawashima, Y., Hanioka, N., Matsumura, M. & Kozuka, H. (1983) Biochim. Biophys. Acta 752, 259-264]. We analyzed the changes in stearoyl-CoA desaturase 1 (SCD1) mRNA to further define the molecular mechanism for the induction of stearoyl-CoA desaturase by peroxisome proliferators. SCD1 mRNA was analyzed from the livers of BALB/c mice that had been fed diets supplemented with clofibrate or gemfibrozil. Clofibrate was found to induce liver SCD1 mRNA levels 3-fold within 6 hr to a maximum of 22-fold in 30 hr. Gemfibrozil administration resulted in a similar induction pattern. This induction is primarily due to an increase in transcription of the SCD1 gene, as shown by nuclear run-on transcription assays and DNA deletion analysis of transfected SCD1-chloramphenicol acetyltransferase fusion genes. The cis-linked response element for peroxisome proliferator-activated receptor (PPAR) was localized to an AGGTCA consensus sequence between base pairs -664 to -642 of the SCD1 promoter. Clofibrate-mediated induction of SCD1 mRNA was shown to be independent of polyunsaturated fatty acids, with peroxisome proliferators and arachidonic acid having opposite effects on SCD1 mRNA levels. Additionally, the activation of SCD1 mRNA by clofibrate was inhibited 77% by cycloheximide administration. Levels of liver beta-actin and albumin mRNAs were unchanged by these dietary manipulations. Our data show that hepatic SCD1 gene expression is regulated by PPARs and suggest that peroxisome proliferators and poly-unsaturated fatty acids act through distinct mechanisms.
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Orally administered antigens induce a state of immunologic hyporesponsiveness termed oral tolerance. Different mechanisms are involved in mediating oral tolerance depending on the dose fed. Low doses of antigen generate cytokine-secreting regulatory cells, whereas high doses induce anergy or deletion. We used mice transgenic for a T-cell receptor (TCR) derived from an encephalitogenic T-cell clone specific for the acetylated N-terminal peptide of myelin basic protein (MBP) Ac-1-11 plus I-Au to test whether a regulatory T cell could be generated from the same precursor cell as that of an encephalitogenic Th1 cell and whether the induction was dose dependent. The MBP TCR transgenic mice primarily have T cells of a precursor phenotype that produce interleukin 2 (IL-2) with little interferon gamma (IFN-gamma), IL-4, or transforming growth factor beta (TGF-beta). We fed transgenic animals a low-dose (1 mg x 5) or high-dose (25 mg x 1) regimen of mouse MBP and without further immunization spleen cells were tested for cytokine production. Low-dose feeding induced prominent secretion of IL-4, IL-10, and TGF-beta, whereas minimal secretion of these cytokines was observed with high-dose feeding. Little or no change was seen in proliferation or IL-2/IFN-gamma secretion in fed animals irrespective of the dose. To demonstrate in vivo functional activity of the cytokine-secreting cells generated by oral antigen, spleen cells from low-dose-fed animals were adoptively transferred into naive (PLJ x SJL)F1 mice that were then immunized for the development of experimental autoimmune encephalomyelitis (EAE). Marked suppression of EAE was observed when T cells were transferred from MBP-fed transgenic animals but not from animals that were not fed. In contrast to oral tolerization, s.c. immunization of transgenic animals with MBP in complete Freund's adjuvant induced IFN-gamma-secreting Th1 cells in vitro and experimental encephalomyelitis in vivo. Despite the large number of cells reactive to MBP in the transgenic animals, EAE was also suppressed by low-dose feeding of MBP prior to immunization. These results demonstrate that MBP-specific T cells can differentiate in vivo into encephalitogenic or regulatory T cells depending upon the context by which they are exposed to antigen.