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      Growing with dinosaurs: natural products from the Cretaceous relict Metasequoia glyptostroboides Hu & Cheng—a molecular reservoir from the ancient world with potential in modern medicine

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          Abstract

          After the sensational rediscovery of living exemplars of the Cretaceous relict Metasequoia glyptostroboides—a tree previously known exclusively from fossils from various locations in the northern hemisphere, there has been an increasing interest in discovery of novel natural products from this unique plant source. This article includes the first complete compilation of natural products reported from M. glyptostroboides during the entire period in which the tree has been investigated (1954–2014) with main focus on the compounds specific to this plant source. Studies on the biological activity of pure compounds and extracts derived from M. glyptostroboides are reviewed for the first time. The unique potential of M. glyptostroboides as a source of bioactive constituents is founded on the fact that the tree seems to have survived unchanged since the Cretaceous era. Since then, its molecular defense system has resisted the attacks of millions of generations of pathogens. In line with this, some recent landmarks in Metasequoia paleobotany are covered. Initial spectral analysis of recently discovered intact 53 million year old wood and amber of Metasequoia strongly indicate that the tree has remained unchanged for millions of years at the molecular level.

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          The war against influenza: discovery and development of sialidase inhibitors.

          The threat of a major human influenza pandemic, in particular from highly aggressive strains such as avian H5N1, has emphasized the need for therapeutic strategies to combat these pathogens. At present, two inhibitors of sialidase (also known as neuraminidase), a viral enzyme that has a key role in the life cycle of influenza viruses, would be the mainstay of pharmacological strategies in the event of such a pandemic. This article provides a historical perspective on the discovery and development of these drugs--zanamivir and oseltamivir--and highlights the value of structure-based drug design in this process.
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            Leukotrienes and lipoxins: structures, biosynthesis, and biological effects.

            Arachidonic acid is released from membrane phospholipids upon cell stimulation (for example, by immune complexes and calcium ionophores) and converted to leukotrienes by a 5-lipoxygenase that also has leukotriene A4 synthetase activity. Leukotriene A4, an unstable epoxide, is hydrolyzed to leukotriene B4 or conjugated with glutathione to yield leukotriene C4 and its metabolites, leukotriene D4 and leukotriene E4. The leukotrienes participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. Recent studies also suggest a neuroendocrine role for leukotriene C4 in luteinizing hormone secretion. Lipoxins are formed by the action of 5- and 15-lipoxygenases on arachidonic acid. Lipoxin A causes contraction of guinea pig lung strips and dilation of the microvasculature. Both lipoxin A and B inhibit natural killer cell cytotoxicity. Thus, the multiple interaction of lipoxygenases generates compounds that can regulate specific cellular responses of importance in inflammation and immunity.
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              Biomolecular characterization and protein sequences of the Campanian hadrosaur B. canadensis.

              Molecular preservation in non-avian dinosaurs is controversial. We present multiple lines of evidence that endogenous proteinaceous material is preserved in bone fragments and soft tissues from an 80-million-year-old Campanian hadrosaur, Brachylophosaurus canadensis [Museum of the Rockies (MOR) 2598]. Microstructural and immunological data are consistent with preservation of multiple bone matrix and vessel proteins, and phylogenetic analyses of Brachylophosaurus collagen sequenced by mass spectrometry robustly support the bird-dinosaur clade, consistent with an endogenous source for these collagen peptides. These data complement earlier results from Tyrannosaurus rex (MOR 1125) and confirm that molecular preservation in Cretaceous dinosaurs is not a unique event.
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                Author and article information

                Affiliations
                [ ]Department of Chemistry and Centre for Pharmacy, University of Bergen, Allégt. 41, 5007 Bergen, Norway
                [ ]University Museum of Bergen, University of Bergen, Thormøhlensgt. 53 A, 5007 Bergen, Norway
                Contributors
                +47 55 58 34 63 , Torgils.Fossen@kj.uib.no
                Journal
                Phytochem Rev
                Phytochem Rev
                Phytochemistry Reviews
                Springer Netherlands (Dordrecht )
                1568-7767
                1572-980X
                22 February 2015
                22 February 2015
                2016
                : 15
                : 161-195
                27065758 4799292 9395 10.1007/s11101-015-9395-3
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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                © Springer Science+Business Media Dordrecht 2016

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