545 research outputs found

    QTL mapping of carrot resistance to leaf blight with connected populations: stability across years and consequences for breeding

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    Combining biparental and multiparental connected population analyses was useful for the identification of 11 QTLs in two new genetic backgrounds of carrot resistance to Alternaria dauci and for breeding recommendations. Leaf blight due to the fungus Alternaria dauci is the major carrot foliar disease worldwide. Some resistance QTLs have been previously identified in one population, but the evaluation of additional genetic backgrounds with higher level of resistance would give opportunities for breeders to combine them by pyramiding. For this purpose, two segregating populations were evaluated twice across 4 years in the same environment (1) to compare the efficiency of the single vs. the connected populations approach for characterizing the new sources of carrot resistance to Alternaria dauci; (2) to evaluate the stability of QTLs over the years; and (3) to give recommendations to breeders for marker-assisted selection. Single and connected analyses were complementary; their combination allowed the detection of 11 QTLs. Connected analyses allowed the identification of common and specific QTLs among the two populations and the most favorable allele at each QTL. Important contrasts between allelic effects were observed with four and five most favorable alleles coming from the two resistant parental lines, whereas two other favorable alleles came from the susceptible parental line. While four QTLs were consistent across years, seven were detected within a single year. The heritabilities for both populations PC2 and PC3 were high (75 and 78 %, respectively), suggesting that the resistance of carrot to A. dauci was little affected by these environmental conditions, but the instability of QTL over years may be due to changing environmental conditions. The complementarity between these parental lines in terms of interesting allelic combinations is also discussed

    Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

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    LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

    Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area

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    The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.062.8% of TH-IR perikarya in humans and 3.260.3% in rats received orexin B-IR afferent contacts. On average, 0.2460.05 and 0.0560.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority(86–88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavierorexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents

    Genetic Changes Over Breeding Generations of \u3cem\u3eFestulolium\u3c/em\u3e

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    Festulolium hybrids are a valuable breeding source for tolerance to abiotic stress and to make grass more persistent under drought and in cold environments. In 2004, the EU Commission enlarged the definition of Festulolium which may now include all hybrids between Lolium sp. and Festuca sp. and not only those between L. multiflorum and F. pratensis. We here report allele frequencies at two unlinked PCR-based marker loci in populations derived from tetraploid (2n=4x=28) L. multiflorum x F. glaucescens hybrids where breeding history enables us to test the effects of selection vs that of genetic drift

    Incorporación de pequeñas secuencias de cine comercial en la enseñanza de las drogodependencias. Ensayo piloto en la asignatura de Toxicología

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    El Grupo de Innovación Docente Orfila, en su propósito por mejorar la calidad de la docencia, está ensayando la utilización del cine con fines didácticos. El material desarrollado en este proyecto consiste en secuencias cortas de películas comerciales de 3 a 5 minutos de duración, que son utilizadas como elementos ilustrativos del proceso de adicción a las a drogas. Se seleccionan escenas de la filmografía y se adecúan al programa docente de la asignatura Toxicología. Se recoge la opinión de los profesores participantes, así como la de los alumnos, mediante una entrevista personal y una encuesta de opinión, respectivamente, de las que se deduce un alto grado de satisfacción

    Clinical guidelines for late-onset Pompe disease

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    English version available at www.neurologia.comHasta 2006, la enfermedad de Pompe o glucogenosis tipo II era una enfermedad incurable y con tratamiento meramente paliativo. El desarrollo de la terapia de sustitución con la enzima α-glucosidasa recombinante humana ha constituido el primer tratamiento específico para esta enfermedad. El objetivo de esta guía es servir de referencia en el manejo de la variedad de inicio tardío de la enfermedad de Pompe, es decir, la que aparece después del primer año de vida. En la guía, un grupo de expertos españoles hace recomendaciones específicas en cuanto a diagnóstico, seguimiento y tratamiento de esta enfermedad. En cuanto al diagnóstico, el método de la muestra en sangre seca es imprescindible como primer paso para el diagnóstico de la enfermedad de Pompe, y el diagnóstico de confirmación de la enfermedad de Pompe debe realizarse mediante un estudio de la actividad enzimática en muestra líquida en linfocitos aislados o mediante el análisis mutacional del gen de la alfa-glucosidasa. En cuanto al tratamiento de la enfermedad con terapia de sustitución enzimática, los expertos afirman que es eficaz en la mejoría o estabilización de la función motora y pulmonar, y debe iniciarse cuando aparezcan los síntomas atribuibles a la enfermedad de PompeBefore 2006, Pompe disease or glycogenosis storage disease type II was an incurable disease whose treatment was merely palliative. The development of a recombinant human alpha-glucosidase enzymatic replacement therapy has become the first specific treatment for this illness. The aim of this guide is to serve as reference for the management of the late-onset Pompe disease, the type of Pompe disease that develops after one year of age. In the guide a group of Spanish experts make specific recommendations about diagnosis, follow-up and treatment of this illness. With regard to diagnosis, the dried blood spots method is essential as the first step for the diagnosis of Pompe disease. The confirmation of the diagnosis of Pompe disease must be made by means of an study of enzymatic activity in isolated lymphocytes or a mutation analysis of the alpha-glucosidase gene. With regard to treatment with enzymatic replacement therapy, the experts say that is effective improving or stabilizating the motor function and the respiratory function and it must be introduced when the first symptoms attributable to Pompe disease appea

    Overexpression of transmembrane protein 168 in the mouse nucleus accumbens induces anxiety and sensorimotor gating deficit

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    Transmembrane protein 168 (TMEM168) comprises 697 amino acid residues, including some putative transmembrane domains. It is reported that TMEM168 controls methamphetamine (METH) dependence in the nucleus accumbens (NAc) of mice. Moreover, a strong link between METH dependence-induced adaptive changes in the brain and mood disorders has been evaluated. In the present study, we investigated the effects of accumbal TMEM168 in a battery of behavioral paradigms. The adeno-associated virus (AAV) Tmem168 vector was injected into the NAc of C57BL/6J mice (NAc-TMEM mice). Subsequently, the accumbal TMEM168 mRNA was increased approximately by seven-fold when compared with the NAc-Mock mice (controls). The NAc-TMEM mice reported no change in the locomotor activity, cognitive ability, social interaction, and depression-like behaviors; however, TMEM168 overexpression enhanced anxiety in the elevated-plus maze and light/dark box test. The increased anxiety was reversed by pretreatment with the antianxiety drug diazepam (0.3 mg/kg i.p.). Moreover, the NAc-TMEM mice exhibited decreased prepulse inhibition (PPI) in the startle response test, and the induced schizophrenia-like behavior was reversed by pretreatment with the antipsychotic drug risperidone (0.01 mg/kg i.p.). Furthermore, accumbal TMEM168 overexpression decreased the basal levels of extracellular GABA in the NAc and the high K+ (100 mM)-stimulated GABA elevation; however, the total contents of GABA in the NAc remained unaffected. These results suggest that the TMEM168-regulated GABAergic neuronal system in the NAc might become a novel target while studying the etiology of anxiety and sensorimotor gating deficits

    Nighttime ozone profiles in the stratosphere and mesosphere by the Global Ozone Monitoring by Occultation of Stars on Envisat

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    The Global Ozone Monitoring by Occultation of Stars (GOMOS) instrument on board the European Space Agency's Envisat satellite measures ozone and a few other trace gases using the stellar occultation method. Global coverage, good vertical resolution and the self-calibrating measurement method make GOMOS observations a promising data set for building various climatologies. In this paper we present the nighttime stratospheric ozone distribution measured by GOMOS in 2003. We show monthly latitudinal distributions of the ozone number density and mixing ratio profiles, as well as the seasonal variations of profiles at several latitudes. The stratospheric profiles are compared with the Fortuin-Kelder daytime ozone climatology. Large differences are found in polar areas and they can be shown to be correlated with large increases of NO2. In the upper stratosphere, ozone values from GOMOS are systematically larger than in the Fortuin-Kelder climatology, which can be explained by the diurnal variation. In the middle and lower stratosphere, GOMOS finds a few percent less ozone than Fortuin-Kelder. In the equatorial area, at heights of around 15–22 km, GOMOS finds much less ozone than Fortuin-Kelder. For the mesosphere and lower thermosphere, there has previously been no comprehensive nighttime ozone climatology. GOMOS is one of the first new instruments able to contribute to such a climatology. We concentrate on the characterization of the ozone distribution in this region. The monthly latitudinal and seasonal distributions of ozone profiles in this altitude region are shown. The altitude of the mesospheric ozone peak and the semiannual oscillation of the number density are determined. GOMOS is also able to determine the magnitude of the ozone minimum around 80 km. The lowest seasonal mean mixing ratio values are around 0.13 ppm. The faint tertiary ozone peak at 72 km in polar regions during wintertime is observed

    Nutritive value of unconventional fibrous ingredients fed to Guinea pigs in the Democratic Republic of Congo

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    peer reviewedThe energy and protein value for Guinea pigs (GP) of 9 forages (7 dicots and 2 grasses) and 5 hay-based diets was determined. The apparent faecal digestibility of dry matter, organic matter, crude protein and energy was measured on GP housed in metabolic cages. The forages and the diets were digested in vitro using pepsin and pancreatin hydrolysis and gas fermentation test to simulate stomach, small intestine and large intestine, respectively. Most of the dicots had high digestible crude protein content (152–201 g/kg DM) and the 2 grasses showed lower values (80–85 g/kg DM). Digestible energy content of the forages ranged between 5.79 to 13.08 MJ/kg DM. None of the forage species or hay-based diets provided sufficient energy to supply the 11.7 MJ/kg metabolic energy requirements. The influence of intestinal fermentation on energy and protein values was highlighted by correlations (P<0.05) between in vivo and in vitro data, including gas fermentation. It is the first time that such relationships are reported in single-stomach animals
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