Biliary lipid secretion in patients with heterozygous familial hypercholesterolemia and combined hyperlipidemia. Influence of bezafibrate and fenofibrate

Serum and biliary lipid metabolism were examined in 13 patients with different types of hyperlipoproteinemia before and after 4 weeks of treatment with either bezafibrate or fenofibrate. In patients with heterozygous familial hypercholesterolemia (FH), bezafibrate (n = 5) and fenofibrate (n = 7) produced a similar significant reduction of total cholesterol, LDL-cholesterol, and triglycerides by 21, 23, and 32%, respectively. In patients with familial combined hyperlipidemia (CHL), only triglycerides decreased markedly. Biliary lipid secretion rates in patients with heterozygous FH were not different from those of young male volunteers, indicating that a reduction of hepatic LDL receptors did not affect hepatic elimination of cholesterol or bile acids. Biliary cholesterol secretion increased significantly from 57 to 75 mg/hr during bezafibrate therapy (n = 8) and from 62 to 71 mg/hr during fenofibrate therapy (n = 9). No consistent change in bile acid or phospholipid secretion was observed. The elevated output of biliary cholesterol increased cholesterol saturation significantly from 147 to 185% and from 152 to 173% during administration of bezafibrate and fenofibrate, respectively. The present study indicates that treatment with bezafibrate or fenofibrate is effective in lowering LDL cholesterol in patients with heterozygous FH, but both drugs increase cholesterol saturation of bile, which might enhance the risk of cholesterol gallstone formation.     

Cross‐resistance of chrysanthemum to western flower thrips,celery leafminer,and two‐spotted spider mite

Chrysanthemum [Chrysanthemum × morifolium Ramat. (Asteraceae)] is one of the economically most important greenhouse ornamentals worldwide. A major constraint in chrysanthemum production is adequate pest management, requiring the use of different tactics, such as improving host plant resistance, in the framework of an integrated pest management (IPM) approach. In this study, we investigated cross‐resistance of chrysanthemum to its three major pests: western flower thrips [Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae)], celery leafminer [Liriomyza trifolii (Burgess) (Diptera: Agromyzidae)], and two‐spotted spider mite [Tetranychus urticae Koch (Acari: Tetranychidae)]. We quantified resistance to each pest by performing greenhouse bioassays with a broad range of chrysanthemum types from commercial germplasm provided by Dutch breeding companies. Considerable variation was detected among the chrysanthemum cultivars in thrips silver damage and growth damage, leafminer damage, measured as number of mines and pupae, and spider mite numbers and damage. We observed significant positive correlations between thrips damage (both silver and growth damage) vs. leafminer numbers (both mines and pupae), and between leafminer numbers (both mines and pupae) vs. spider mite numbers. Our results indicate an overlap in resistance to all three herbivores. The important implications of this result for chrysanthemum breeding are discussed.     

Structural long-term changes at mushroom body input synapses

How does the sensory environment shape circuit organization in higher brain centers? Here we have addressed the dependence on activity of a defined circuit within the mushroom body of adult Drosophila. This is a brain region receiving olfactory information and involved in long-term associative memory formation. The main mushroom body input region, named the calyx, undergoes volumetric changes correlated with alterations of experience. However, the underlying modifications at the cellular level remained unclear. Within the calyx, the clawed dendritic endings of mushroom body Kenyon cells form microglomeruli, distinct synaptic complexes with the presynaptic boutons of olfactory projection neurons. We developed tools for high-resolution imaging of pre- and postsynaptic compartments of defined calycal microglomeruli. Here we show that preventing firing of action potentials or synaptic transmission in a small, identified fraction of projection neurons causes alterations in the size, number, and active zone density of the microglomeruli formed by these neurons. These data provide clear evidence for activity-dependent organization of a circuit within the adult brain of the fly.     

Rootletin forms centriole-associated filaments and functions in centrosome cohesion

After duplication of the centriole pair during S phase, the centrosome functions as a single microtubule-organizing center until the onset of mitosis, when the duplicated centrosomes separate for bipolar spindle formation. The mechanisms regulating centrosome cohesion and separation during the cell cycle are not well understood. In this study, we analyze the protein rootletin as a candidate centrosome linker component. As shown by immunoelectron microscopy, endogenous rootletin forms striking fibers emanating from the proximal ends of centrioles. Moreover, rootletin interacts with C-Nap1, a protein previously implicated in centrosome cohesion. Similar to C-Nap1, rootletin is phosphorylated by Nek2 kinase and is displaced from centrosomes at the onset of mitosis. Whereas the overexpression of rootletin results in the formation of extensive fibers, small interfering RNA-mediated depletion of either rootletin or C-Nap1 causes centrosome splitting, suggesting that both proteins contribute to maintaining centrosome cohesion. The ability of rootletin to form centriole-associated fibers suggests a dynamic model for centrosome cohesion based on entangling filaments rather than continuous polymeric linkers.     

Performance of reciprocally sown populations of Senecio vulgaris from ruderal and agricultural habitats

Senecio vulgaris from ruderal habitats may colonise crop fields and persist in the new environment. Persistence may occur through phenotypic plasticity or genetic differentiation. In the presence of genetic variation, differential responses of life history traits to selection may lead to local adaptation. A reciprocal seed transplant experiment was conducted to determine environmental and genetic variation of life history traits in S. vulgaris from ruderal and agricultural habitats, and whether infection by the rust Puccinia lagenophorae is a selection factor in S. vulgaris populations. Emergence, growth and fecundity showed environmental as well as genetic variation, as shown by a significant site and origin effect. However, there was no evidence of local adaptation, as indicated by the absence of significant origin by site interactions. Genetic variation in emerging seedling numbers seems to be important for S. vulgaris, an annual plant which has no means other than seed production for propagation. Seedling survival was solely under environmental control stressing the importance of stochastic events for plant mortality. Most S. vulgaris from ruderal sites showed reduced growth, but still reached reproduction, suggesting that S. vulgaris is following the plastic strategy of a stress tolerator to endure unfavourable environments. Plants at most agricultural sites behaved like r-strategists, exploiting a productive environment for rapid plant growth and maximising reproduction. Emergence, survival, growth and fecundity were higher at the agricultural sites. Infection by the rust occurred at all sites, with the highest incidence at the agricultural sites, and was solely determined by the environment. A higher incidence did not result in an increased disease impact on plant growth and reproduction nor did it affect survival of S. vulgaris. Although the majority of life-history traits studied showed phenotypic and genetic variation, which can both be subject to natural selection, no adaptation of S. vulgaris to its local environment was detected.     

Identification of Chlorogenic Acid as a Resistance Factor for Thrips in Chrysanthemum

Western flower thrips (Frankliniella occidentalis) has become a key insect pest of agricultural and horticultural crops worldwide. Little is known about host plant resistance to thrips. In this study, we investigated thrips resistance in chrysanthemum (Dendranthema grandiflora). We identified thrips-resistant chrysanthemums applying bioassays. Subsequently, nuclear magnetic resonance (NMR)-based metabolomics was applied to compare the metabolome of thrips-resistant and -susceptible chrysanthemums. NMR facilitates wide-range coverage of the metabolome. We show that thrips-resistant and -susceptible chrysanthemums can be discriminated on basis of their metabolomic profiles. Thrips-resistant chrysanthemums contained higher amounts of the phenylpropanoids chlorogenic acid and feruloyl quinic acid. Both phenylpropanoids are known for their inhibitory effect on herbivores as well as pathogens. Thus, chlorogenic and feruloyl quinic acid are the compounds of choice to improve host plants resistance to thrips in ornamentals and crops. The effect of chlorogenic acid on thrips was further studied in bioassays with artificial diets. These experiments confirmed the negative effects on thrips. Our results prove NMR to be an important tool to identify different metabolites involved in herbivore resistance. It constitutes a significant advance in the study of plant-insect relationships, providing key information on the implementation of herbivore resistance breeding strategies in plants.