Paths reunited: initiation of the classical and lectin pathways of complement activation

Understanding the structural organisation and mode of action of the initiating complex of the classical pathway of complement activation (C1) has been a central goal in complement biology since its isolation almost 50 years ago. Nevertheless, knowledge is still incomplete, especially with regard to the interactions between its subcomponents C1q, C1r and C1s that trigger activation upon binding to a microbial target. Recent studies have provided new insights into these interactions, and have revealed unexpected parallels with initiating complexes of the lectin pathway of complement: MBL–MASP and ficolin–MASP. Here, we develop and expand these concepts and delineate their implications towards the key aspects of complement activation via the classical and lectin pathways

Dihydroisocoumarins, Naphthalenes, and Further Polyketides from Aloe vera and A. plicatilis: Isolation, Identification and Their 5-LOX/COX-1 Inhibiting Potency

The present study aims at the isolation and identification of diverse phenolic polyketides from Aloe vera (L.) Burm.f. and Aloe plicatilis (L.) Miller and includes their 5-LOX/COX-1 inhibiting potency. After initial Sephadex-LH20 gel filtration and combined silica gel 60- and RP18-CC, three dihydroisocoumarins (nonaketides), four 5-methyl-8-C-glucosylchromones (heptaketides) from A. vera, and two hexaketide-naphthalenes from A. plicatilis have been isolated by means of HSCCC. The structures of all polyketides were elucidated by ESI-MS and 2D 1H/13C-NMR (HMQC, HMBC) techniques. The analytical/preparative separation of 3R-feralolide, 3′-O-β-d-glucopyranosyl- and the new 6-O-β-d-glucopyranosyl-3R-feralolide into their respective positional isomers are described here for the first time, including the assignment of the 3R-configuration in all feralolides by comparative CD spectroscopy. The chromones 7-O-methyl-aloesin and 7-O-methyl-aloeresin A were isolated for the first time from A. vera, together with the previously described aloesin (syn. aloeresin B) and aloeresin D. Furthermore, the new 5,6,7,8-tetrahydro-1-O-β-d-glucopyranosyl- 3,6R-dihydroxy-8R-methylnaphtalene was isolated from A. plicatilis, together with the known plicataloside. Subsequently, biological-pharmacological screening was performed to identify Aloe polyketides with anti-inflammatory potential in vitro. In addition to the above constituents, the anthranoids (octaketides) aloe emodin, aloin, 6′-(E)-p-coumaroyl-aloin A and B, and 6′-(E)-p-coumaroyl-7-hydroxy-8-O-methyl-aloin A and B were tested. In the COX-1 examination, only feralolide (10 µM) inhibited the formation of MDA by 24%, whereas the other polyketides did not display any inhibition at all. In the 5-LOX-test, all aloin-type anthranoids (10 µM) inhibited the formation of LTB4 by about 25–41%. Aloesin also displayed 10% inhibition at 10 µM in this in vitro setup, while the other chromones and naphthalenes did not display any activity. The present study, therefore, demonstrates the importance of low molecular phenolic polyketides for the known overall anti-inflammatory activity of Aloe vera preparations

iObserve: Integrated Observation and Modeling Techniques to Support Adaptation and Evolution of Software Systems

The goal of iObserve is to develop methods and tools to support evolution and adaptation of long-lived software systems. Future long-living software systems will be engineered using third-party software services and infrastructures. Key challenges for such systems will be caused by dynamic changes of deployment options on cloud platforms. Third-party services and infrastructures are neither owned nor controlled by the users and developers of service-based systems. System users and developers are thus only able to observe third-party services and infrastructures via their interface, but are not able to look into the software and infrastructure that provides those services. In this technical report, we summarize our results of four activities to realize a complete tooling around Kieker, Palladio, and MAMBA, supporting performance and cost prediction, and the evaluation of data privacy in context of geo-locations. Furthermore, the report illustrates our efforts to extend Palladio