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991.
Annika Frank Francisco Meza-Arriagada Cristian O. Salas Christian Espinosa-Bustos Holger Stark 《Bioorganic & medicinal chemistry》2019,27(14):3194-3200
Inspired by marine compounds the derivatization of the natural pyrrolo[2,3-d]pyrimidine lead scaffold led to a series of novel compounds targeting the histamine H3 receptor. The focus was set on improved binding towards the receptor and to establish an initial structure-activity relationship for this compound class based on the lead structure (compound V, Ki value of 126 nM). As highest binding affinities were found with 1,4-bipiperidines as basic part of the ligands, further optimization was focused on 4-([1,4′-bipiperidin]-1′-yl)-pyrrolo[2,3-d]pyrimidines. Related pyrrolo[2,3-d]pyrimidines that were isolated from marine sponges like 4-amino-5-bromopyrrolo[2,3-d]pyrimidine (compound III), showed variations in halogenation pattern, though in a next step the impact of halogenation at 2-position was evaluated. The chloro variations did not improve the affinity compared to the dehalogenated compounds. However, the simultaneous introduction of lipophilic cores with electron-withdrawing substitution patterns in 7-position and dehalogenation at 2-position (11b, 12b) resulted in compounds with significantly higher binding affinities (Ki values of 7 nM and 6 nM, respectively) than the initial lead structure compound V. The presented structures allow for a reasonable structure-activity relationship of pyrrolo[2,3-d]pyrimidines as histamine H3 receptor ligands and yielded novel lead structures within the natural compound library against this target. 相似文献
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Design and visualization of second‐generation cyanoisoindole‐based fluorescent strigolactone analogs
Melissa Van Overtveldt Lukas Braem Sylwia Struk Anna M. Kaczmarek Franois‐Didier Boyer Rik Van Deun Kris Gevaert Sofie Goormachtig Thomas S. A. Heugebaert Christian V. Stevens 《The Plant journal : for cell and molecular biology》2019,98(1):165-180
Strigolactones (SLs) are a family of terpenoid allelochemicals that were recognized as plant hormones only a decade ago. They influence a myriad of both above‐ and below‐ground developmental processes, and are an important survival strategy for plants in nutrient‐deprived soils. A rapidly emerging approach to gain knowledge on hormone signaling is the use of traceable analogs. A unique class of labeled SL analogs was constructed, in which the original tricyclic lactone moiety of natural SLs is replaced by a fluorescent cyanoisoindole ring system. Biological evaluation as parasitic seed germination stimulant and hypocotyl elongation repressor proved the potency of the cyanoisoindole strigolactone analogs (CISAs) to be comparable to the commonly accepted standard GR24. Additionally, via a SMXL6 protein degradation assay, we provided molecular evidence that the compounds elicit SL‐like responses through the natural signaling cascade. All CISAs were shown to exhibit fluorescent properties, and the high quantum yield and Stokes shift of the pyrroloindole derivative CISA‐7 also enabled in vivo visualization in plants. In contrast to the previously reported fluorescent analogs, CISA‐7 displays a large similarity in shape and structure with natural SLs, which renders the analog a promising tracer to investigate the spatiotemporal distribution of SLs in plants and fungi. 相似文献
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996.
Christian A. Tryon 《Evolutionary anthropology》2019,28(5):267-282
The Middle to Later Stone Age (MSA/LSA) transition is a prominent feature of the African archeological record that began in some places ~30,000–60,000 years ago, historically associated with the origin and/or dispersal of “modern” humans. Unlike the analogous Middle to Upper Paleolithic transition in Eurasia and associated Neanderthal extinction, the African MSA/LSA record remains poorly documented, with its potential role in explaining changes in the behavioral diversity and geographic range of Homo sapiens largely unexplored. I review archeological and biogeographic data from East Africa, show regionally diverse pathways to the MSA/LSA transition, and emphasize the need for analytical approaches that document potential ancestor‐descendent relationships visible in the archeological record, needed to assess independent invention, population interaction, dispersal, and other potential mechanisms for behavioral change. Diversity within East Africa underscores the need for regional, rather than continental‐scale narratives of the later evolutionary history of H. sapiens. 相似文献
997.
Laurent Vandepaer Julie Cloutier Christian Bauer Ben Amor 《Journal of Industrial Ecology》2019,23(3):709-725
Stationary batteries are projected to play a role in the electricity system of Switzerland after 2030. By enabling the integration of surplus production from intermittent renewables, energy storage units displace electricity production from different sources and potentially create environmental benefits. Nevertheless, batteries can also cause substantial environmental impacts during their manufacturing process and through the extraction of raw materials. A prospective consequential life cycle assessment (LCA) of lithium metal polymer and lithium‐ion stationary batteries is undertaken to quantify potential environmental benefits and drawbacks. Projections are integrated into the LCA model: Energy scenarios are used to obtain marginal electricity supply mixes, and projections about the battery performances and the recycling process are sourced from the literature. The roles of key parameters and methodological choices in the results are systematically investigated. The results demonstrate that the displacement of marginal electricity sources determines the environmental implications of using batteries. In the reference scenario representing current policy, the displaced electricity mix is dominated by natural gas combined cycle units. In this scenario, the use of batteries generates environmental benefits in 12 of the 16 impact categories assessed. Nevertheless, there is a significant reduction in achievable environmental benefits when batteries are integrated into the power supply system in a low‐carbon scenario because the marginal electricity production, displaced using batteries, already has a reduced environmental impact. The direct impacts of batteries mainly originate from upstream manufacturing processes, which consume electricity and mining activities related to the extraction of materials such as copper and bauxite. 相似文献
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A core eco‐evolutionary aim is to better understand the factors driving the diversification of functions in ecosystems. Using phylogenetic, trophic, and functional information, we tested whether trophic habits (i.e. feeding guilds) affect lineage and functional diversification in two major radiations of reef fishes. Our results from wrasses (Labridae) and damselfishes (Pomacentridae) do not fully support the ‘dead‐end’ hypothesis that specialisation leads to reduce speciation rates because the tempo of lineage diversification did not substantially vary among guilds in both fish families. Our findings also demonstrate a tight relationship between trophic habits and functional roles held by fish in reef ecosystems, which is not associated with a variation in the tempo of functional diversification among guilds. By illustrating the pivotal importance of the generalist feeding strategy during the evolutionary history of reef fishes, our study emphasises the role of this feeding guild as a reservoir for future diversity. 相似文献