Search results for "Sini"
showing 10 items of 351 documents
Complex vein systems as a data source in tectonics: An example from the Ugab Valley, NW Namibia
2014
Abstract Neoproterozoic metaturbidites in the Lower Ugab Domain, Namibia, contain a complex network of four sets of quartz-calcite veins, overprinted by km-scale folds associated with four regional foliations. The veins formed by fluid overpressure predating the main deformation. Deformation structures developed at the junction of two mobile belts during the assembly of Gondwana, the NS Kaoko Belt, and the EW trending Damara Belt. Km-scale NS trending folds were initiated during EW constriction in the Kaoko Belt, while their further development and all subsequent events are related to constriction in the EW-Damara Belt, with coeval sinistral strike slip in the Kaoko Belt. Deformation of the…
Paleoclimate and bubonic plague: a forewarning of future risk?
2010
Background Human cases of plague (Yersinia pestis) infection originate, ultimately, in the bacterium's wildlife host populations. The epidemiological dynamics of the wildlife reservoir therefore determine the abundance, distribution and evolution of the pathogen, which in turn shape the frequency, distribution and virulence of human cases. Earlier studies have shown clear evidence of climatic forcing on contemporary plague abundance in rodents and humans. Results We find that high-resolution palaeoclimatic indices correlate with plague prevalence and population density in a major plague host species, the great gerbil (Rhombomys opimus), over 1949-1995. Climate-driven models trained on these…
There is no general model for occlusal kinematics in conodonts
2014
Knowledge of conodont element function is based largely on analysis of morphologically similar P-1 elements of few comparatively closely related species known from abundant articulated remains. From these, a stereotypical pattern of rotational occlusion has been inferred, leading to the suggestion that this may represent a general model for ozarkodinin P-1 elements at the very least. We test the generality of this occlusal model through functional analysis of Pseudofurnishius murcianus P-1 elements which, though superficially similar to homologous elements in gnathodids, evolved their platform morphology independently, through a different mode of morphogenesis, and in a different topologica…
Design of novel artemisinin-like derivatives with cytotoxic and anti-angiogenic properties
2010
Abstract Artemisinins are plant products with a wide range of medicinal applications. Most prominently, artesunate is a well tolerated and effective drug for treating malaria, but is also active against several protozoal and schistosomal infections, and additionally exhibits anti-angiogenic, anti-tumorigenic and anti-viral properties. The array of activities of the artemisinins, and the recent emergence of malaria resistance to artesunate, prompted us to synthesize and evaluate several novel artemisinin-like derivatives. Sixteen distinct derivatives were therefore synthesized and the in vitro cytotoxic effects of each were tested with different cell lines. The in vivo anti-angiogenic proper…
Abstract 5109: Beyond malaria: Second career of artesunate as cancer drug
2017
Abstract More than a decade ago, we initiated a research program on the molecular pharmacology of phytochemicals derived from Chinese medicinal herbs. Bioactive plant extracts have been fractionated by chromatographic techniques. We isolated bioactive compounds and elucidated their chemical structures by nuclear magnetic resonance and mass spectrometry. A promising compounds was artemisinin from Artemisia annua L. and its semisynthetic compound artesunate. Artemisinin and artesunate are anti-malarial drugs. Our data indicated profound activity against cancer cells, but also against various viruses, Schistosoma, Trypanosoma, and even plant crown gall tumors. To elucidate the molecular mode o…
The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-κB) pathway by targeting RelA/p65.
2015
Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of standard antiviral therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy is based on the exploitation of cell-directed signaling inhibitors. The broad antiinfective drug artesunate (ART) offers additional therapeutic options such as oral bioavailability and low levels of toxic side-effects. Here, novel ART-derived compounds including dimers and trimers were synthesized showing further improvements over the parental drug. Antiviral activity and mechanistic aspects were determined leading to the followi…
Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum
2012
Malaria causes millions of death cases per year. Since Plasmodium falciparum rapidly develops drug resistance, it is of high importance to investigate potential drug targets which may lead to novel rational therapy approaches. Here we report on the interaction of translationally controlled tumor protein of P. falciparum (PfTCTP) with the anti-malarial drug artemisinin. Furthermore, we investigated the crystal structure of PfTCTP. Using mass spectrometry, bioinformatic approaches and surface plasmon resonance spectroscopy, we identified novel binding sites of artemisinin which are in direct neighborhood to amino acids 19-46, 108-134 and 140-163. The regions covered by these residues are know…
Differential interactions of the broad spectrum drugs artemisinin, dihydroartemisinin and artesunate with serum albumin
2013
Artemisinin is a drug, widely used in malaria treatment. As the binding affinity of artemisinin and its derivatives dihydroartemisinin and artesunate to blood serum proteins might influence the effectiveness of the drug, binding of artemisinin and derivatives to serum albumin was studied under near physiological conditions. Binding kinetics indicate a simple, single-step association process for all artemisinin derivatives. The determined changes in enthalpy and entropy upon drug binding clearly indicate that hydrophobic forces are most important for artemisinin and dihydroartemisinin binding, whereas binding of artesunate is governed by both hydrophilic and hydrophobic forces. Key residues,…
New insights from recently migrated CROP multichannel seismic data at the outermost Calabrian arc accretionary wedge (Ionian sea)
2011
This study addresses selected aspects of the stratigraphic-structural setting of the outermost Calabrian Arc accretionary wedge and underlines relationships between structural development and Messinian evaporite stratigraphy through the analysis of re-processed CROP multichannel seismic reflection profiles. A detailed seismostratigraphic analysis, calibrated with P-velocities compiled by previous works, images a general bipartition of the Messinian evaporite deposits: the transparent «lower subunit» appears to have undergone ductile-flow deformation», with the development of salt-cored thrusting structures, and the layered «upper subunit» appears to be characterized by brittle deformation. …
Enzyme-linked immunosorbent assay for detection of Aeromonas hydrophila serogroup O:19
2006
An enzyme-linked immunosorbent assay has been developed for the detection of Aeromonas hydrophila serogroup O:19 isolated from epizootics in eels. The enzyme-linked immunosorbent assay specificity was confirmed after testing A. hydrophila O:19 and non-O:19 strains from different origins, as well as other Aeromonas species and other fish pathogens such as Vibrio vulnificus biotype 2, V. furnisii, V. damsela, Yersinia ruckerii and Edwardsiella tarda. The detection limits for A. hydrophila O:19 cells were around 10(4)-10(5) cells/well. Artificially infected eels were analyzed and the immunodetection was confirmed by cultural methods. With this methodology A. hydrophila O:19 was successfully de…