5 research outputs found
Reversible modulation of circadian time with chronophotopharmacology
The circadian clock controls daily rhythms of physiological processes. The presence of the clock mechanism throughout the body is hampering its local regulation by small molecules. A photoresponsive clock modulator would enable precise and reversible regulation of circadian rhythms using light as a bio-orthogonal external stimulus. Here we show, through judicious molecular design and state-of-the-art photopharmacological tools, the development of a visible light-responsive inhibitor of casein kinase I (CKI) that controls the period and phase of cellular and tissue circadian rhythms in a reversible manner. The dark isomer of photoswitchable inhibitor 9 exhibits almost identical affinity towards the CKIα and CKIδ isoforms, while upon irradiation it becomes more selective towards CKIδ, revealing the higher importance of CKIδ in the period regulation. Our studies enable long-term regulation of CKI activity in cells for multiple days and show the reversible modulation of circadian rhythms with a several hour period and phase change through chronophotopharmacology
Autonomous Agents Modelling Other Agents: A Comprehensive Survey and Open Problems
Much research in artificial intelligence is concerned with the development of
autonomous agents that can interact effectively with other agents. An important
aspect of such agents is the ability to reason about the behaviours of other
agents, by constructing models which make predictions about various properties
of interest (such as actions, goals, beliefs) of the modelled agents. A variety
of modelling approaches now exist which vary widely in their methodology and
underlying assumptions, catering to the needs of the different sub-communities
within which they were developed and reflecting the different practical uses
for which they are intended. The purpose of the present article is to provide a
comprehensive survey of the salient modelling methods which can be found in the
literature. The article concludes with a discussion of open problems which may
form the basis for fruitful future research.Comment: Final manuscript (46 pages), published in Artificial Intelligence
Journal. The arXiv version also contains a table of contents after the
abstract, but is otherwise identical to the AIJ version. Keywords: autonomous
agents, multiagent systems, modelling other agents, opponent modellin
Effects of cryptochrome-modulating compounds on circadian behavioural rhythms in zebrafish
Bile salts of vertebrates: structural variation and possible evolutionary significance[S]
Biliary bile salt composition of 677 vertebrate species (103 fish, 130 reptiles, 271 birds, 173 mammals) was determined. Bile salts were of three types: C27 bile alcohols, C27 bile acids, or C24 bile acids, with default hydroxylation at C-3 and C-7. C27 bile alcohols dominated in early evolving fish and amphibians; C27 bile acids, in reptiles and early evolving birds. C24 bile acids were present in all vertebrate classes, often with C27 alcohols or with C27 acids, indicating two evolutionary pathways from C27 bile alcohols to C24 bile acids: a) a ‘direct’ pathway and b) an ‘indirect’ pathway with C27 bile acids as intermediates. Hydroxylation at C-12 occurred in all orders and at C-16 in snakes and birds. Minor hydroxylation sites were C-1, C-2, C-5, C-6, and C-15. Side chain hydroxylation in C27 bile salts occurred at C-22, C-24, C-25, and C-26, and in C24 bile acids, at C-23 (snakes, birds, and pinnipeds). Unexpected was the presence of C27 bile alcohols in four early evolving mammals. Bile salt composition showed significant variation between orders but not between families, genera, or species. Bile salt composition is a biochemical trait providing clues to evolutionary relationships, complementing anatomical and genetic analyses