Genetic study of cognitive function

Dissecting the genetics of Alzheimer’s disease (AD) and Parkinson’s disease (PD) has contributed significantly to our understanding of the pathogenesis of neurodegeneration in these two complex disorders. For AD, three highly penetrant genes (APP, PSEN1 and PSEN2) and one susceptibility gene (APOE) have been identified. For PD, seven genes (SNCA, Parkin, UCHL1, NR4A2, DJ1, PINK1 and LRRK2) have been found. These genes explain only a small proportion of AD and PD patients and are mostly associated with an early onset presentation of the disease. APOE remains the only common gene, which increases the risk of both rare early and late onset AD. The ongoing challenge is to unravel the genetics of the most frequent forms of these complex disorders. In the present paper, we briefl y review the state of the art in the genetics of AD and PD. We also discuss the prospects of finding new genes associated with common forms of these diseases in light of two hypotheses concerning the genetic variation of complex diseases: common disease/ common variants and common disease/rare variants

Diet digestibility and production performance in dairy goats consuming plant oils

The aim of this study was to investigate the effects of differently unsaturated vegetable oils added to dairy goat diets on apparent digestibility and performance traits. Twelve Malagueña goats were randomly assigned to one of four treatments: no oil (CONTROL), 48 g/d of high oleic sunflower oil (GAO), regular sunflower oil (RSFO) or linseed oil (LIN). The basal diet was made of alfalfa hay and a pelleted concentrate, which included the respective oil and chromium as indicator. The experimental period lasted 21 days. The digestibility of dietary components, except for fat, did not differ between treatments (P > 0.05). Oil inclusion in the diet significantly (P < 0.05) increased fat digestibility. There were no significant differences (P > 0.05) in dry matter intake, milk yield and milk composition between treatments. It was concluded that moderate amounts of unsaturated plant oils can be added to dairy goat diets without negative effects on diet digestibility or performance traits

Lipid metabolism in ruminants

El objetivo de este trabajo fue revisar algunos aspectos del metabolismo lipídico y características relevantes de la grasa de la carne y la leche de los rumiantes. Los ácidos grasos disponibles para la absorción en el intestino delgado de los rumiantes proceden de los alimentos y los microorganismos ruminales, y son mayoritariamente ácidos grasos saturados y no esterificados debido a la digestión microbiana ruminal. Los ácidos grasos absorbidos que tienen menos de 12 carbonos son vertidos directamente a la vena porta y transportados al hígado unidos a la albúmina sérica; el resto son esterificados e incorporados a lipoproteínas de muy baja densidad y quilomicrones que se transportan por vía linfática hasta el torrente sanguíneo para su distribución a los tejidos. El hígado de los rumiantes tiene menor importancia en el metabolismo lipídico que el de los monogástricos, pero adquiere especial relevancia en situaciones de balance energético negativo en las que la alteración del metabolismo hepático de los lípidos puede provocar graves patologías. Los depósitos grasos distintos de la musculatura están constituidos casi exclusivamente por triglicéridos y son la principal reserva de energía del organismo. Por el contrario, la grasa intramuscular posee distintas proporciones de fosfolípidos y triglicéridos en función del grado de engrasamiento. Los fosfolípidos de las membranas celulares son el lugar preferente de deposición de los ácidos grasos poliinsaturados disponibles. La composición de la grasa láctea varía en función del origen de los ácidos grasos: ácidos grasos de cadena larga de origen alimentario o movilizados desde el tejido adiposo, o ácidos grasos de cadena corta y media sintetizados in situ a partir de acetato y betahidroxibutirato. La mayor parte de los ácidos grasos incorporados a los triglicéridos lácteos son captados de la sangre. La importante contribución de los ácidos grasos de la dieta consumida por los rumiantes a los lípidos de sus productos ofrece la posibilidad de modificar el contenido de los ácidos grasos de la carne y, sobre todo, la leche en un sentido favorable para la salud de los consumidores.In this paper, key aspects of lipid metabolism and characteristics of ruminants’ meat and milk fat were reviewed. Fatty acids available for absorption in the small intestine of ruminants are from dietary and microbial origin and, because of microbial digestion in the rumen, are mainly nonsterified saturated fatty acids. Short chain fatty acids (less than 12 carbon atoms) are absorbed into the bloodstream, bound to serum albumin and transported to the liver through the portal vein. Medium and long chain fatty acids are esterified upon their absorption and transported via lymph to the bloodstream as chylomicrons and very low density lipoproteins, to be used by the different tissues. In ruminants, the liver has a minor role in lipid metabolism compared with monogastrics, but it is especially relevant in situations of intense negative energy balance when the hepatic metabolism of lipids may be altered causing severe pathologies. Fat depots other than intramuscular depots are composed mainly of triglycerides and are the major energy reserve of the body. However, the proportion of phospholipids and triglycerides in the intramuscular fat depends on the degree of fatness. The cell membrane phospholipids are the preferred site of deposition of available polyunsaturated fatty acids. Milk fat composition depends on the origin of the fatty acids: long chain fatty acids from dietary origin or mobilized from adipose tissue, or medium and short chain fatty acids synthesized in situ from acetate and betahydroxybutyrate. Most fatty acids incorporated into milk triglycerides are taken from the blood. The major contribution of dietary fatty acids to meat and, specially, milk fatty acids offers the possibility of changing the fatty acid profile of ruminant products to promote human consumer health

Límites nutricionales para dietas de cabras lecheras en crecimiento

El objetivo del presente trabajo fue revisar el consumo de materia seca y las necesidades nutritivas de cabras lecheras de reposición estabuladas para establecer límites nutricionales aplicables a la formulación de dietas por programación lineal a mínimo coste. El diseño de dietas nutricionalmente adecuadas y económicas requiere que el nutricionista estime correctamente el consumo de materia seca y forraje y los aportes y las necesidades de nutrientes. La bibliografía revisada sugiere que el consumo total de materia seca de las cabras oscila entre los límites físico y fisiológico impuestos por la capacidad del tracto digestivo y las necesidades energéticas diarias. El efecto de llenado digestivo puede relacionarse con los carbohidratos estructurales de la dieta, mientras la saciedad metabólica se relaciona con la concentración energética de la dieta. El consumo mínimo de forraje necesario para mantener la salud ruminal es bajo, mientras que el consumo máximo de forraje está determinado probablemente por el contenido de fibra neutrodetergente de la dieta. Los aportes y las necesidades de energía y proteína calculadas según los dos sistemas de valoración más modernos son similares, por lo que es indistinto usar cualquiera de ambos para optimizar dietas. Las propuestas recientes para el cálculo de los aportes y las necesidades de calcio y fósforo ofrecen una mayor precisión

Effect of fat sources on fiber digestion in ruminants

El objetivo del presente trabajo fue revisar el efecto de la inclusión de fuentes de grasa no protegidas sobre la digestión de la fibra en los rumiantes. Es bien conocido que el aporte de grasa extra en forma de fuentes de grasa no protegidas a la dieta puede afectar negativamente a los microorganismos del rumen y, en consecuencia, a la digestión microbiana de la dieta. La bibliografía revisada indica que la fibra es el único componente de la dieta cuya digestibilidad es reducida en ocasiones. Este efecto es menos frecuente cuando el contenido de grasa extra en la dieta no supera el 4% con independencia del grado de insaturación, forma de presentación y procesado de la fuente de grasa. En los trabajos en que se observó reducción de la digestibilidad de la fibra aunque la inclusión de grasa extra en la dieta fue inferior al 4%, el forraje mayoritario aportado fue ensilado, o se utilizaron fuentes de grasa ricas en ácidos grasos poliinsaturados de más de 20 carbonos. Cuando la grasa extra se incluye por encima del 4% en la dieta, la reducción de la digestibilidad de la fibra es más frecuente pero no existe una relación clara entre los resultados observados y las características de la fuente de grasa o de la dieta. En ocasiones, la ausencia de efectos negativos de la grasa extra sobre la digestibilidad total de la fibra puede ser explicada porque la disminución de la digestión ruminal es compensada totalmente por la digestión en los tramos posteriores del tracto digestivo. El efecto negativo de las fuentes de grasa no protegidas sobre la digestibilidad de la fibra se relaciona con el efecto tóxico que los ácidos grasos insaturados de cadena larga tienen sobre las bacterias fibrolíticas y los protozoos ruminales, aunque el mecanismo de acción no ha sido aclarado.The aim of this paper was to review the effect of unprotected dietary lipid sources on fiber digestion in ruminants. It is well known that extra fat included in the diet in the form of unprotected fat sources sometimes can negatively affect rumen microorganisms and alter the microbial digestion of the diet. Reviewed literature points out fiber is the only dietary component whose digestibility can be decreased. This effect is less common when extra fat is included in the diet up to 4% regardless of unsaturation degree, and type or processing of the fat source. Decreased fiber digestibility observed in some studies where extra fat was lower than 4% could be due to the inclusion of silage as the main forage in the diet, or the use of fat sources rich in polyunsaturated fatty acids over 20 carbons. When extra fat is included in the diet above 4%, decreased fiber digestibility is more common but there is not clear relationship between the observed effect and the characteristics of the fat source or the diet. In some studies, the lack of negative effects of extra fat on total fiber digestibility could be explained because digestion in the lower digestive tract completely compensated for the decrease of rumen digestion. Decreased fiber digestibility when unprotected fat sources are included in ruminant diets is related to the toxic effect that long chain unsaturated fatty acids have on rumen fibrolytic bacteria and protozoa, although the exact mechanism of action has not been determined ye

Predicting keratinocyte carcinoma in patients with actinic keratosis: development and internal validation of a multivariable risk-prediction model

Background: Patients with actinic keratosis (AK) are at increased risk for developing keratinocyte carcinoma (KC) but predictive factors and their risk rates are unknown. Objectives: To develop and internally validate a prediction model to calculate the absolute risk of a first KC in patients with AK. Methods: The risk-prediction model was based on the prospective population-based Rotterdam Study cohort. We hereto analysed the data of participants with at least one AK lesion at cohort baseline using a multivariable Cox proportional hazards model and included 13 a priori defined candidate predictor variables considering phenotypic, genetic and lifestyle risk factors. KCs were identified by linkage of the data with the Dutch Pathology Registry. Results: Of the 1169 AK participants at baseline, 176 (15·1%) developed a KC after a median follow-up of 1·8 years. The final model with significant predictors was obtained after backward stepwise selection and comprised the presence of four to nine AKs [hazard ratio (HR) 1·68, 95% confidence interval (CI) 1·17–2·42], 10 or more AKs (HR 2·44, 95% CI 1·65–3·61), AK localization on the upper extremities (HR 0·75, 95% CI 0·52–1·08) or elsewhere except the head (HR 1·40, 95% CI 0·98–2·01) and coffee consumption (HR 0·92, 95% CI 0·84–1·01). Evaluat

The importance of being zero

2018 International Symposium on Symbolic and Algebraic Computation (ISSAC), July 2018, New York, NY, United StatesWe present a deterministic algorithm for deciding if a polynomial ideal, with coefficients in an algebraically closed field K of characteristic zero, of which we know just some very limited data, namely:the number n of variables, and some upper bound for the geometric degree of its zero set in Kn, is or not the zero ideal. The algorithm performs just a finite number of decisions to check whether a point is or not in the zero set of the ideal. Moreover, we extend this technique to test, in the same fashion, if the elimination of some variables in the given ideal yields or not the zero ideal. Finally, the role of this technique in the context of automated theorem proving of elementary geometry statements, is presented, with references to recent documents describing the excellent performance of the already existing prototype version, implemented in GeoGebra.Ministerio de Economía y CompetitividadEuropean Regional Development Fun

CARACTERISTICAS DE CEPAS CHILENAS DE Pyrenochaeta lycopersici Y PERSPECTIVAS DE CONTROL BIOLOGICO

Raíz corchosa es una de las principales enfermedades que afecta al cultivo de tomate que se produce bajo invernadero frío en Chile. En esta investigación se entregan antecedentes referentes a las principalescaracterísticas reproductivas de su agente causal, Pyrenochaeta lycopersici, como: picnidios, conidióforos y conidios. Además, antecedentes sobre la estrategia de control biológico de esta enfermedad. En base a estudios preliminares, se determinó a Trichoderma harzianum, como el taxa más promisorio (según cultivos duales).Se caracterizaron cepas de ambas especies de acuerdo a crecimiento micelial a diferentes temperaturas, pH, y salinidad (NaCl). Finalmente, se efectuó un ensayo bajo condiciones controladas de invernadero, destacándose la cepa Th11 como la más promisoria en el biocontrol de este patógeno

The relationship between transgenerational acquired resistance and global DNA methylation in Arabidopsis

Progeny of heavily diseased plants develop transgenerational acquired resistance (TAR). In Arabidopsis, TAR can be transmitted over one stress-free generation. Although DNA methylation has been implicated in the regulation of TAR, the relationship between TAR and global DNA methylation remains unknown. Here, we characterised the methylome of TAR-expressing Arabidopsis at different generations after disease exposure. Global clustering of cytosine methylation revealed TAR-related patterns in the F3 generation, but not in the F1 generation. The majority of differentially methylated positions (DMPs) occurred at CG context in gene bodies. TAR in F3 progeny after one initial generation of disease, followed by two stress-free generations, was lower than TAR in F3 progeny after three successive generations of disease. This difference in TAR effectiveness was proportional to the intensity of differential methylation at a sub-set of cytosine positions. Comparison of TAR-related DMPs with previously characterised cytosine methylation in mutation accumulation lines revealed that ancestral disease stress preferentially acts on methylation-labile cytosine positions, but also extends to methylation-stable positions. Thus, the TAR-related impact of ancestral disease extends beyond stochastic variation in DNA methylation. Our study has shown that the Arabidopsis epigenome responds globally to disease in previous generations and we discuss its contribution to TAR