Bioactive secondary metabolites from the endophytic fungus Chaetomium sp. isolated from Salvia officinalis growing in Morocco

This study reports the chemical investigation and cytotoxic activity of the secondary metabolites produced by the endophytic fungus Chaetomium sp. isolated from Salvia officinalis growing in Morocco. This plant was collected from the Beni-Mellal Mountain in Morocco and belongs to the Lamiaceae family and is named in Morocco 'Salmia'. The endophytic fungus Chaetomium sp. was isolated from the tissues of the stem of this plant. The fungal strain was identified by PCR. The crude organic extract of the fungal strain was proven to be active when tested for cytotoxicity against L5178Y mouse lymphoma cells. Chemical investigation of the secondary metabolites showed that cochliodinol is the main component beside isocochliodinol. The structures of the isolated compounds were determined on the basis of NMR analysis (1H, 13C, COSY and HMBC) as well as by mass spectrometry using ESI (Electron Spray Ionisation) as source

The Evolution of Extracellular Matrix

We present a perspective on the molecular evolution of the extracellular matrix (ECM) in metazoa that draws on research publications and data from sequenced genomes and expressed sequence tag libraries. ECM components do not function in isolation, and the biological ECM system or “adhesome” also depends on posttranslational processing enzymes, cell surface receptors, and extracellular proteases. We focus principally on the adhesome of internal tissues and discuss its origins at the dawn of the metazoa and the expansion of complexity that occurred in the chordate lineage. The analyses demonstrate very high conservation of a core adhesome that apparently evolved in a major wave of innovation in conjunction with the origin of metazoa. Integrin, CD36, and certain domains predate the metazoa, and some ECM-related proteins are identified in choanoflagellates as predicted sequences. Modern deuterostomes and vertebrates have many novelties and elaborations of ECM as a result of domain shuffling, domain innovations and gene family expansions. Knowledge of the evolution of metazoan ECM is important for understanding how it is built as a system, its roles in normal tissues and disease processes, and has relevance for tissue engineering, the development of artificial organs, and the goals of synthetic biology

Marine niedere Tiere und Mikrobionten als Rohstoffquellen zur Gewinnung von Arzneistoffen. Projekt 1.1: Isolierung, Charakterisierung und klinische Anwendung von bioaktiven Substanzen aus marinen niederen Tieren Abschlussbericht

State of the present knowledge: Sponges as well as corals are major sources of potential pharmaceutical compounds. Rationale and aim of the study: Source for the sponges as starting material: Northern Adriatic Sea near Rovinj (Croatia). Source for the corals: Red Sea (Egypt). Low molecular weight compounds to be studied: We focused on the isolation and characterization of bioactive compounds from sponges and corals. Further class of compounds to be studied: Those compounds which are produced by the sponges and corals and which ultimately attract bacteria can be grouped to the class of proteins, and represent lectins. Also this latter class of substances has been analyzed. Method used for the study: Application of modern molecular biological-, cell biological and immunological techniques applicable for the identification and purification of bioactive compounds. Results: Low molecular weight compounds: Two compounds have been isolated and characterized: One sterol from the coral Nephthya laevis: The material, the soft coral Nephthya laevis, was collected from the Red Sea. The bioactive compound was isolated and the structure elucidated. Those analyses revealed the new compound: 22-methylene-3-#beta#-hydroxycholest-5-ene; the short name is Nepthsterol. Bioactivity: Low effect on cell proliferation of tumor cells; strong neuroprotective effect on cortical neurons (obtained from rats). One terpene from the coral Sarcophyton glaucum. Also this substance was purified and characterized. The analyses revealed a substance from the class of lactonditerpenes, and the compound was termed Sarcophytolid. Bioactivity: Strong effect on proliferation of tumor cells; no neuroprotective effect on neurons; strong effect on proliferation on human endothelial cells. Conclusion: Three products have been developed to a direction that an application appears to be realistic - however further basic studies are needed. Publications: six. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(83,11) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Chemoprophylaxe und Chemotherapie bei Prion-Infektionen Schlussbericht

As stated at the beginning of the program in the frame of this project in 1994, it is still today true that there is no effective treatment of Prion-diseases available. Our group discovered for the first time that the initiation of apoptosis of neuronal cells in Prion-diseases is based on an increase of Ca"2"+. Consequently, we succeeded also for the first time in formulating a strategy which might ultimately lead to a therapy of such diseases. Based on the data we elaborated and according to the 'foerderpolitischen Ziele' the above mentioned proposal was submitted; it had the aim to elucidate an effective chemoprophylaxis and -therapy for Prion-diseases. Two compounds - which might be clinically applicable - have been studied by us: - Memantine (an NMDA-antagonist) and - Flupirtine (a novel neuroprotective drug). Concerning Memantine a preclinical animal-study was not possible due to unfavourable pharmacokinetics. The mode of action of Flupirtine was elucidated. A novel site was detected - modulation of Bcl-2-expression. These data have been confirmed by other groups - also using animal studies. Essentially on the basis of our data a phase 3 clinical trial with the aim of a treatment of Creutzfeld-Jakob-disease was started; drug: Flupirtine. This study is the first of its kind worldwide. Taken together, our data gathered hitherto in the frame of this project are - to our judgement - international of great importance and impact. The data have been published in international high ranking Journals. A further proposal for financial support of our work on the elucidation of further strategies to treat Prion-diseases with the project title 'Entwicklung neuroprotektiver Substanzen zur Behandlung von Prion-Erkrankungen: Zweite Generation [Development of neuroprotective drugs for the treatment of Prion-diseases: Second generation]' was rejected. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(60,45) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Kultivierung von Schwammzellen in vitro als Basis fuer eine kontrollierte und effiziente Gewinnung von bioaktiven Substanzen Abschlussbericht

State of the Art: Sponges represent the richest source for natural products. Until recently, sponges could be obtained only by diving or collecting. No group succeeded to cultivate tissue fragments or even cells in vitro. Situation 1998: Until 1998 no method was available to establish a proliferating cell culture. Results: The breakthrough came after the application of molecular biological techniques. In our approach is was possible - for the first time - to cultivate in vitro of proliferating culture for more than 5 months; the cells were termed Primmorphes. Organisms: Sponge Suberites domuncula and Geodia cydonium. Both species grow in aquaria in Mainz all the year around. Marker for sponge cells: Suitable molecular tools have been worked out. Isolation of a cDNA-library from S. domuncula and other sponges. Isoaltion of suitable cDNAs: First cDNAs, which code for bioactive compounds have been isolated cDNAs. First bioactive proteins and low molecular weight compounds have been produced in culture. (orig.)Available from TIB Hannover: DtF QN1(84,25) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Siliceous deep-sea sponge Monorhaphis chuni: A potential paleoclimate archive in ancient animals

The deep-sea sponge Monorhaphis chuni forms giant basal spicules, which can reach lengths of 3 m; they represent the largest biogenic silica structures on Earth that is formed from an individual metazoan. The spicules offer a unique opportunity to record environmental change of past oceanic and climatic conditions. A giant spicule collected in the East China Sea in a depth of 1110 m was investigated. The oxygen isotopic composition and Mg/Ca ratios determined along center-to-surface segments are used as geochemical proxies for the assessment of seawater paleotemperatures. Calculations are based on the assumption that the calculated temperature near the surface of the spicule is identical with the average ambient temperature of 4 degrees C. A seawater temperature of 1.9 degrees C is inferred for the beginning of the lifespan of the Monorhaphis specimen. The temperature increases smoothly to 2.3 degrees C, to be followed by sharply increased and variable temperatures up to 6-10 degrees C. In the outer part of the spicule, the inferred seawater temperature is about 4 degrees C. The lifespan of the spicule can be estimated to 11,000 +/- 3000 years using the long-term trend of the inferred temperatures fitted to the seawater temperature age relationships since the Last Glacial Maximum. Specimens of Monorhaphis therefore represents one the oldest living animals on Earth. The remarkable temperature spikes of the ambient seawater occurring 9500-3100 years B.P. are explained by discharges of hydrothermal fluids in the neighborhood of the spicule. The irregular lamellar organization of the spicule and the elevated Mn concentrations during the high-temperature growth are consistent with a hydrothermal fluid input. (C) 2012 Elsevier B.V. All rights reserved