ABSTRACT
En lineas de conejos reproductivamente cerradas, criadas con generaciones discretas, existe una fuerte asociacion entre el año-estacion (AE) y los niveles de consanguinidad (F). Estudios realizados anteriormente mostraron que, cuando AE y F son considerados como efectos fijos en un modelo, la heredabilidad y la tendencia genetica se sobreestiman. El objetivo del trabajo fue investigar las consecuencias de considerar AE como fijo (M1) o aleatorio (M2) sobre la seleccion de animales. Se utilizaron 15671 registros correspondientes al numero de destetados de la linea A, del Departamento de Ciencia Animal de la Universidad Politecnica de Valencia, España. Los modelos fueron comparados en base a: los ordenamientos de los valores geneticos aditivos estimados en cada generacion y la respuesta esperada a la seleccion. Se plantearon seis escenarios segun intensidades de seleccion. En cada uno se estimo la correlacion de Spearman y se calculo el porcentaje de discordancia (D) entre los animales elegidos por M2 y no por M1. La respuesta a la seleccion para los animales escogidos por M1 o M2, fue estimada como la pendiente de la recta de regresion entre las medias de los valores geneticos predichos por M2 a traves de las generaciones. A medida que disminuyo la presion de seleccion, aumentaron las correlaciones de Spearman, disminuyendo los D. Aunque, a nivel generacion ambos estimadores no mantuvieron siempre la misma relacion. Las respuestas a la seleccion estimadas fueron similares para los animales seleccionados por M1 o M2, con lo cual no se esperan diferencias entre ambos modelos respecto a la seleccion.
In close reproductive lines of rabbits reared in discrete generations, there is a strong association between the year-season (AE) and the levels of consanguinity (F). Previous studies have shown that when AE and F were considered as fixed effects in a model, the heritability and the genetic tendency were overestimated. The objective of this work was to investigate the consequences of considering AE as either a fixed (M1) or random (M2) effect on the selection of animals. A total of 15,671 records corresponding to the number of rabbits weaned in line A, from the Department of Animal Science of the Polytechnic University of Valencia, Spain, were used. The comparison of models was based on the rankings of the estimated additive genetic values in each generation and the expected response to the selection. Six scenarios were proposed, varying in selection intensities. In each one, the Spearman correlation was estimated and the percentage of discordance (D) between the animals chosen for M2 but not for M1 was calculated. The response to selection for the animals chosen by either M1 or M2, was estimated as the slope of the regression line between the means of the genetic values predicted by M2 through generations. As the selection pressure decreased, the Spearman correlations increased, decreasing the D. However, at the generation level, both estimators did not always maintain that relationship. The estimated responses to selection were similar when the selection was based on estimated breeding values obtained by using either M1 or M2. Therefore, no differences are expected between both models with respect to selection.
ABSTRACT
El traumatismo encéfalo craneano (TEC) es un problema de salud de distribución mundial, y es especialmente prevalente en la población adulta joven. Es característica la presencia de uno o más focos de daño, que luego progresan hacia áreas inicialmente no lesionadas, mediante cascadas de respuesta inflamatoria, excitotoxicidad, condiciones de falla energética, y la participación de la glía amplificando la respuesta tisular al daño inicial. Esta progresión es, en teoría, susceptible de una intervención terapéutica. Sin embargo, hasta ahora todos los estudios con fármacos neuroprotectores han fracasado, no existiendo un tratamiento especí-fico efectivo. Los resultados negativos se explican en parte por el empleo de una estrategia centrada solo en las neuronas, sin considerar otras células participantes, u otros mecanismos patogénicos. Para cambiar este panorama, es necesario re-enfocar el problema a través de una mejor comprensión de los mecanismos que determinan la progresión del daño. En esta revisión discutiremos los principales mecanismos biológicos involucrados en la progresión del daño tisular post-trauma. Se aborda la fisiopatología general de los tipos de traumatismos, mecanismos celulares del daño secundario incluyendo inflamación, apoptosis, tumefacción celular, excitoxicidad, y participación de la glía en la propagación del daño. Se destaca el papel de laglía en cada uno de los mecanismos celulares mencionados. Se incluyen algunas aproximaciones terapéuticas relacionadas con los mecanismos descritos. Se finaliza con un diagrama general que resume los principales aspectos discutido (AU)
Traumatic brain injury (TBI) is a worldwide health problem that is especially prevalent in young adults. It is characterized by one or more primary injury foci, with secondary spread to initially not compromised areas via cascades of inflammatory response, excitotoxicity, energy failure conditions, and amplification of the original tissue injury by glia. In theory, such progression of injury should be amenable to management. However, all neuroprotective drug trials have failed, and specific treatments remain lacking. These negative results can be explained by a neuron centered approach, excluding the participation of other cell types and pathogenic mechanisms. To change this situation, it is necessary to secure a better understanding of the biological mechanisms determining damage progression or spread. We discuss the biological mechanisms involved in the progression of post-trauma tissue damage, including the general physiopathology of TBI and cellular mechanisms of secondary damage such as inflammation, apoptosis, cell tumefaction, excitotoxicity, and the role of glia in damage propagation. We highlight the role of glia in each cellular mechanism discussed. Therapeutic approaches related to the described mechanisms have been included. The discussion is completed with a working model showing the convergence of the main topics (AU)
Subject(s)
Humans , Craniocerebral Trauma/physiopathology , Brain Injury, Chronic/physiopathology , Apoptosis , Neurotoxins/pharmacokinetics , Neuroglia , Risk Factors , Disease ProgressionABSTRACT
Traumatic brain injury (TBI) is a worldwide health problem that is especially prevalent in young adults. It is characterized by one or more primary injury foci, with secondary spread to initially not compromised areas via cascades of inflammatory response, excitotoxicity, energy failure conditions, and amplification of the original tissue injury by glia. In theory, such progression of injury should be amenable to management. However, all neuroprotective drug trials have failed, and specific treatments remain lacking. These negative results can be explained by a neuron centered approach, excluding the participation of other cell types and pathogenic mechanisms. To change this situation, it is necessary to secure a better understanding of the biological mechanisms determining damage progression or spread. We discuss the biological mechanisms involved in the progression of post-trauma tissue damage, including the general physiopathology of TBI and cellular mechanisms of secondary damage such as inflammation, apoptosis, cell tumefaction, excitotoxicity, and the role of glia in damage propagation. We highlight the role of glia in each cellular mechanism discussed. Therapeutic approaches related to the described mechanisms have been included. The discussion is completed with a working model showing the convergence of the main topics.
