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Protein aggregation is the principal component of numerous protein misfolding pathologies termed proteinopathies, such as Alzheimer’s disease, Parkinson’s disease, prion disease, and AA amyloidosis with unmet treatment needs. Protein aggregation inhibitors have great potential for the prevention and treatment of proteinopathies. Here we report the development of an automated real-time microliter-scale high throughput screening (MSHTS) system for amyloid aggregation inhibitors using quantum-dot nanoprobes. Screening 504 crude extracts and 134 low molecular weight aromatic compounds revealed the relationship of amyloid-β (Aβ) aggregation inhibitory activities of plant extracts using a plant-based classification. Within the eudicots, rosids, Geraniales and Myrtales showed higher activity. Screening low molecular weight aromatic compounds demonstrated that the structure of tropolone endows it with potential Aβ aggregation inhibitory activity. The activity of the most active tropolone derivative was higher than that of rosmarinic acid. MSHTS also identified three chaperone molecules as tau aggregation inhibitors. These results demonstrate that our automated MSHTS system is a novel and robust tool that can be adapted to a wide range of compounds and aggregation-prone polypeptides.

Eight chlorinated alkylresorcinols, monochasiol A–H (1–8), were isolated from the fruiting bodies of Dictyostelium monochasioides. Compounds 1–8 were synthesized to confirm their structures and to obtain sufficient material for performing biological tests. Monochasiol A (1) selectively inhibited the concanavalin A-induced interleukin-2 production in Jurkat cells, a human T lymphocyte cell line. Monochasiols were biogenetically synthesized by the combination of biosynthetic enzymes relating to the principal polyketides, MPBD and DIF-1, produced by Dictyostelium discoideum.

Bird populations were censused in relation to habitat size and vegetation in Obihiro, Hok-kaido, during the breeding season (late April to early June) and non-breeding season (early November to early February), 1986-88. Five parks of urban area (plots A, B, C, D, E) and two wood islands of suburban area (plots F, G) were selected as census plots. A total of 38 bird species were recorded in breeding season and 30 species in non-breeding season. Most of them were forest birds or birds prefering open habitats, and shrub-grassland birds were scarce. In breeding season, the abundant bird species included Motacilla alba, Carduelis sinica, Passer montanus and Corvus corone, which were common species in urban areas of Hokkaido. Common bird species in parks with high tree density were forest bird prefering wide variety of habitats or sparse woods such as Dendorocopos major, Hypsipetes amaurotis, Turdus chrysolaus, Aegithalos caudatus, Parus palustris, Parus major, Coccothrauste coccotraustes, and Sturnus philippensis. In non-breeding season, the main species were D. major, H. amaurotis, Turdus naumanni, A. caudatus, P. palustris, Parus ater, P. major, Sitta europaea, Passer montanus and C. corone in all parks and wood islands. In breeding season, the number of total and forest bird species, forest bird density and bird species diversity H' increased with increasing tree density and canopy cover. In non-breeding season, the number of forest bird species increased and the number of non-forest bird species decreased with incresing tree density. There was no signi-ficant relationship between bird species diversity and vegetation variables because of increasing diversity even in plots with low tree density in non-breeding season. Both in breeding and non-breeding seasons, per cent ground cover did not influence the number of bird species and bird species diversity because the ground cover consisted of lawn in most cases. In urbanized area, parks provide an important habitat for birds.