Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E

Apolipoprotein E is a multifunctional protein synthesized by hepatocytes and macrophages. Plasma apoE is largely liver-derived and known to regulate lipoprotein metabolism. Macrophage-derived apoE has been shown to reduce the progression of atherosclerosis in mice. We tested the hypothesis that liver-derived apoE could directly induce regression of pre-existing advanced atherosclerotic lesions without reducing plasma cholesterol levels. Aged low density lipoprotein (LDL) receptor-deficient (LDLR(-/-)) mice were fed a western-type diet for 14 weeks to induce advanced atherosclerotic lesions. One group of mice was sacrificed for evaluation of atherosclerosis at base line, and two other groups were injected with a second generation adenoviruses encoding human apoE3 or a control empty virus. Hepatic apoE gene transfer increased plasma apoE levels by 4-fold at 1 week, and apoE levels remained at least 2-fold higher than controls at 6 weeks. There were no significant changes in plasma total cholesterol levels or lipoprotein composition induced by expression of apoE. The liver-derived human apoE gained access to and was retained in arterial wall. Compared with base-line mice, the control group demonstrated progression of atherosclerosis; in contrast, hepatic apoE expression induced highly significant regression of advanced atherosclerotic lesions. Regression of lesions was accompanied by the loss of macrophage-derived foam cells and a trend toward increase in extracellular matrix of lesions. As an index of in vivo oxidant stress, we quantitated the isoprostane iPF(2 alpha)-VI and found that expression of apoE markedly reduced urinary, LDL-associated, and arterial wall iPF(2 alpha)-VI levels. In summary, these results demonstrate that liver-derived apoE directly induced regression of advanced atherosclerosis and has anti-oxidant properties in vivo that may contribute to its anti-atherogenic effects.     

A neural model of the dynamic activation of memory

We study an Attractor Neural Network that stores natural concepts, organized in semantic classes. The concepts are represented by distributed patterns over a space of attributes, and are related by both semantic and episodic associations. While semantic relations are expressed through an hierarchical coding over the attribute space, episodic links are realized via specific synaptic projections. Due to dynamic thresholds expressing neuronal fatigue, the network's behavior is characterized by convergence toward the concept patterns on a short time scale, and by transitions between the various patterns on a longer time scale. In its baseline, undamaged state, the network manifests semantic, episodic, and random transitions, and demonstrates the phenomen of priming. Modeling possible pathological changes, we have found that increasing the noise level or the rate of neuronal fatigue decreases the frequency of semantic transitions. When neurons characterized by large synaptic connectivity are deleted, semantic transitions decay before the episodic ones, in accordance with the findings in patients with Alzheimer's disease.     

The development of property rights in biotechnology

The translation of biological theory into engineering (biotechnology) has resulted in the development of novel products and processes. Some of these products are living organisms, usually containing unique genetic arrangements not found in nature. The extension of legal protection to products and processes was required in order for biotechnology to become an unexceptional way in which to do business. The American experience with biotechnology, repeated elsewhere, is demonstrated to have proceeded first through the negotiation of obstacles in administrative law and second through challenges to property law. This outcome for the regulatory management of biotechnology and the legal protection of its products may be interpreted as a function of a cultural bias for scientific authority and progress ideology.     

The macrolepidoptera of farm woodlands: determinants of diversity and community structure

The Farm Woodland Scheme, which provided incentives to convert agricultural land to timber production, contained an implicit assumption that farm woodlands produce important benefits for wildlife. The moth fauna of 18 farm woodlands in the Vale of York was surveyed between May and November 1991. The aims were twofold. The first was to determine if there were benefits for moth species diversity. The second was to ascertain whether concepts of island biogeography and the plant species richness of the woods were related to the moth species composition.Eleven families, 214 species and over 16 000 individuals of moths were recorded. Classification of the species presence/absence matrix indicated that small woods (less than 1ha) did not have characteristic woodland moth communities. Woods larger than 5ha were judged to be more valuable for the long-term conservation of woodland moth diversity. The best predictor of moth species richness was the herbaceous plant species richness within woodlands. Species richness of the family Geometridae was positively related to woodland area, as well as to woodland shape (compact shapes being preferable to elongated shapes). Characteristic woodland species are influenced by isolation (less isolated woods being richer in species). The implications of different powers of dispersal between moth families are discussed. Farm woodlands will be of more value for the conservation of the Macrolepidoptera if they are large, compact and incorporate remnants of existing woodland with extant herbaceous vegetation. These should be factors which are taken into consideration when providing incentives to establish and manage farm woodlands.     

Oral dosing of insects with feeding deterrent compounds

A preliminary assessment was made of a variety of approaches to dosing insects with compounds that normally deter feeding. Enclosing water-soluble compounds in liposomes has promise for strong deterrents, although in drinking assays many deterrents lose their potency anyway. Microencapsulating compounds by embedding them in a polymer matrix to form spheres without a true barrier wall may have masked deterrency of a lipophilic compound, but did not adequately mask the taste of water-soluble compounds. Microencapsulation with gelatin was shown to work with lipid-soluble dye and the capsule walls appear to be broken down very rapidly after ingestion. Coating fine particles with beeswax did not successfully mask the deterrence of quinine, but has value with compounds insoluble in lipids. Starch coating can be effective for insects lacking salivary amylase. Molecular encapsulation of grindelic acid in cyclodextrin masked its deterrency to Schistocerca americana. Nymphs fed this material through the second and third instars showed an increase in development time during the third instar without any corresponding reduction in consumption rate. Behavioral approaches to administering deterrent compounds include drinking and habituation. Some compounds that reduce consumption of leaf material were taken in drinking water in amounts sufficient to give relevant doses in one or two drinks daily. Pseudaletia unipuncta larvae fed nicotine-treated wheat through the fifth and sixth instars ate less than control larvae during the first 24 h of the experiment but showed no reduction in consumption after that period. A one-day increase in development time was attributed to the one-day habituation period. More work is needed on the release of taste-masked compounds in the gut.

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Resumé Des essais préliminaires ont porté sur les différentes techniques de dosage de produits qui normalement inhibent la prise de nourriture. L'isolement des composés hydrosolubles dans des liposomes a donné des résultats prometteurs pour les dissuadants puissants, bien qu'au cours d'absorptions expérimentales de liquide beaucoup de dissuadants aient perdu de leur efficacité. La microencapsulation, en les enfouissant dans une matrice de polymère pour former des sphères sans véritable paroi, peut avoir masqué le pouvoir dissuadant des produits lipophiles, mais n'a pas masqué suffisamment le goût des produits hydrosolubles. La microencapsulation dans des capsules de gélatine a été efficace avec les colorants liposolubles, la paroi de la capsule semblant détruite très rapidement après ingestion. Le revêtement de fines particules par de la cire n'a pas masqué efficacement l'effet dissuasif de la quinine, mais a été valable avec les produits insolubles dans les lipides. L'encapsulation moléculaire de l'acide grindellique dans de la cyclodextrine a masqué son effect dissuasif pour [?]Schistocerca gregaria. Les larves ont mangé le tout pendant les second et troisième stades et ont présenté un ralentissement du développement pendant le troisième stade sans diminuation de la consommation. L'étude comportementale de l'administration de produits dissuasifs comprend l'action de boire et l'accoutumance. Certains produits qui réduisent la consommation de feuilles ont été absorbés en quantités suffisantes avec l'eau de boisson pour donner des doses significatives avec une ou deux prises de liquide par jour. Des larves de Pseudaletia unipuncta alimentées avec du blé traité à la nicotine pendant les cinquième et sixième stades, ont consommé moins que les témoins, mais seulement pendant les 24 premières heures de l'expérience. La prolongation d'un jour, de la durée de développement, a été attribuée au temps nécessaire à l'accoutumance.

     

Development of the axillary bud complex in Echinocystis lobata (Cucurbitaceae): interpreting the cucurbitaceous tendril

In the Cucurbitaceae, the tendrils, coiling organs used for climbing and mechanical support, are part of an axillary bud complex (ABC). Although the morphological nature of tendrils and the branching pattern of the ABC in the Cucurbitaceae have been much studied, their homology remains unresolved, with hypothesized candidates being the leaf, flower, stem, or stem-leaf combination. We used Echinocystis lobata as a model to study the early ontogeny of the ABC with epi-illumination microscopy and serial resin sections. The ABC produces four structures (proximal to distal, relative to the subtending leaf) as the result of two successive subdivisions: an inflorescence of staminate flowers, a solitary pistillate flower, a lateral bud, and a tendril. The first separates the tendril primordium from the continuation of the ABC, and the second separates the staminate inflorescence and the ABC. The pistillate flower apparently forms between the staminate inflorescence and the lateral bud. Because there is no subtending leaf during these subdivisions and the first lateral appendages in the resulting primordia arise in the same plane, we conclude that the tendril and other organs formed by the ABC are lateral branches of equal morphological value. This study is the basis for continuing comparative and functional morphological studies.     

INFLUENCE OF VARIOUS EXPOSURE PERIODS ON THE BIOMASS AND CHLOROPHYLL A OF CLADOPHORA GLOMERATA (CHLOROPHYTA)1

The biomass of Cladophora glomerata (L.) Kütz. was estimated at selected sites in the Colorado River between Glen Canyon Dam, Arizona, and River Kilometer 354. C. glomerata biomass was significantly higher at sites above Lees Ferry (25 km downstream from the Dam) than sites below the Ferry. Biomass and chlorophyll a were significantly reduced when C. glomerata was subjected to one-time exposures to the atmosphere for 12 daylight h in more. Repeated 12/12 h and 24/24 h (exposure/submergence) cycles over a two-week period also showed a significant reduction in biomass. The adaptations of C. glomerata to “stranding” during regulated flows are discussed.     

Muscle development in Atlantic salmon (Salmo salar) embryos and the effect of temperature on muscle cellularity

Salmon eggs were incubated at 5, 8 or 11° C from fertilization to hatching. At Gorodilov stages 25, 27, 29, 31 and 33 transverse sections of whole embryos (at somite level 10–15) were prepared for histochemistry and electron microscopy. At every stage up to hatching, cross–sectional areas of the embryos were not different between temperatures, and from stage 27 onwards there was also no difference in the ratio of white to red muscle. However, there were more muscle fibres but of smaller average diameter in both the red and white muscle for the colder temperature embryos. At hatching there were also more nuclei (per cross–section) in the colder embryos but more nuclei per muscle fibre in the warmer embryos. In all cases the 8° C embryos were intermediate between 5 and 11° C embryos in their muscle parameters. Fast and slow muscle fibres could only be distinguished in the embryos by alkali–stable ATPase reactions. Succinic dehydrogenase activity was low in embryonic fish. No differences between the temperature groups were detected in the histochemical reactions for either ATPase or succinic dehydrogenase activities.     

Overexpression of apolipoprotein O does not impact on plasma HDL levels or functionality in human apolipoprotein A-I transgenic mice

Apolipoprotein (apo) O is a newly discovered apolipoprotein preferentially contained within HDL; however, currently, no data are available on the (patho)physiological effects of apoO. Therefore, the present study assessed the impact of apoO overexpression on (i) plasma lipids and lipoproteins as well as on (ii) HDL functionality. Human apoO was overexpressed by means of recombinant adenovirus (AdhapoO) in human apoA-I transgenic mice, a humanized mouse model of HDL metabolism. AdhapoO substantially increased apoO in plasma and within HDL. However, plasma triglycerides, phospholipids, total cholesterol and HDL cholesterol did not change. HDL size distribution, lipid composition and the apoA-I and the apoO distribution over the different HDL fractions separated by FPLC remained unaltered. Furthermore, enrichment of HDL with apoO did not impact on HDL functionality assessed in four independent ways, namely (i) stimulation of cholesterol efflux from macrophage foam cells, (ii) protection against LDL oxidation, (iii) anti-inflammatory activity on endothelial cells, and (iv) induction of vasodilation in isolated aortic rings ex vivo as a measure of stimulating vascular NO production. These results demonstrate that although overexpression of apoO results in a substantial enrichment of HDL particles with this novel apolipoprotein, apoO does not impact the plasma lipoprotein profile or HDL functionality.