Bilobalide modulates serotonin-controlled behaviors in the nematode Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>Dysfunctions in the serotonergic system have been implicated in several neurological disorders such as depression. Elderly individuals who have been diagnosed with clinical depression show elevated cases of neurodegenerative diseases. This has led to suggestions that modulating the serotonin (5-HT) system could provide an alternative method to current therapies for alleviating these pathologies. The neuroprotective effects of bilobalide <it>in vitro </it>have been documented. We aim to determine whether bilobalide affects the 5-HT system in the nematode <it>C. elegans</it>. The wild type worms, as well as well-characterized 5-HT mutants, were fed with bilobalide in a range of concentrations, and several 5-HT controlled behaviors were tested.</p> <p>Results</p> <p>We observed that bilobalide significantly inhibited 5-HT-controlled egg-laying behavior in a dose-dependent manner, which was blocked in the 5-HT receptor mutants (<it>ser-4, mod-1</it>), but not in the 5-HT transporter (<it>mod-5</it>) or synthesis (<it>tph-1</it>) mutants. Bilobalide also potentiated a 5-HT-controlled, experience-dependent locomotory behavior, termed the enhanced slowing response in the wild type animals. However, this effect was fully blocked in 5-HT receptor <it>mod-1 </it>and dopamine defective <it>cat-2 </it>mutants, but only partially blocked in <it>ser-4 </it>mutants. We also demonstrated that acetylcholine transmission was inhibited in a transgenic <it>C. elegans </it>strain that constitutively expresses Aβ, and bilobalide did not significantly affect this inhibition.</p> <p>Conclusion</p> <p>These results suggest that bilobalide may modulate specific 5-HT receptor subtypes, which involves interplay with dopamine transmission. Additional studies for the function of bilobalide in neurotransmitter systems could aid in our understanding of its neuroprotective properties.</p

Regional wind-field study in complex terrain during summer sea-breeze conditions

A regional-scale data base, consisting of wind and temperature data for June and July of 1977, was developed for the greater San Francisco Bay Area and eastward to the Central Valley. Continuous meteorological measurements were made in the area of a windy pass (Patterson Pass) 3 km east of Lawrence Livermore Laboratory. This area was chosen because of its complex terrain and importance as a downwind topographic feature affecting the dispersal of possible accidental atmospheric releases from the Laboratory and as an area of high wind-energy potential. The results of this study provided the following: (1) a data base, including over 50 stations for use in numerical wind-field regional-scale-model validation; (2) characterization of summer sea breese oscillations of approx. 6 and 12 days (this analysis is useful in calculating wind-power persistence and in understanding summer sea-breeze mechanisms in the Bay Area); and (3) successful application of an optical space-averaging wind sensor over a 1-km path across a pass to provide long-path averaged data more suitable for regional, numerical wind-field models with kilometre-size grid elements

Low-Temperature Direct Wafer Bonding

The breakthrough of directwafer bondingwas achieved with siliconon-insulator (SOI) allowing for high-power and high-frequency electronics, microelectronics components with low energy consumption. After this, several bonding techniques have been developed (e.g. silicon direct bonding, anodic bonding) and are being developed (e.g. low-temperature plasma-assisted direct bonding) to achieve hybrid components, as III-V semiconductors on silicon-based substrates, monolithic integration of optoelectronic devices with high-speed silicon integrated circuits, three-dimensional stacking of integrated circuits (ICs) or circuits transfer onto a variety of substrates. An overview of more recent activities on several techniques for attaining low-temperature bonding is presented

Overview of Aspergillus allergens

Fungi in general and, Aspergillus fumigatus (A. fumigatus) in particular, are able to produce complex patterns of IgE-binding molecules. Robotics-based high throughput screening of A. fumigatus cDNA libraries displayed on phage surfaces revealed at last 81 different sequences encoding structures potentially able to bind to serum IgE of sensitised individuals suffering from A. fumigatus-related complications. Although not all of these allergens have been characterised in detail, A. fumigatus still represents the best investigated allergenic source. A total of 23 A. fumigatus allergens are recorded by the official allergen list of the International Union of Immunological Societies (http://www.allergen.org) and this is by far the longest allergen list reported for a single allergenic source. The IgE-binding molecules include species-specific as well as phylogenetically highly conserved cross-reactive structures and such with unknown function. A subset of cDNAs have been used to produce and characterise the corresponding recombinant allergens which have proven to be useful diagnostic reagents allowing specific detection of A. fumigatus sensitisation and differential diagnosis of allergic bronchopulmonary aspergillosis. Structures highly conserved through different species like manganese-dependent superoxide dismutase, P2 acidic ribosomal protein, cyclophilins and thioredoxins induce, beyond sensitisation, IgE antibodies able to cross-react with the corresponding homologous self-antigens. The frequently observed cross-reactivity is traceable back to shared discontinuous B-cell epitopes as shown by detailed analyses of the crystal structures