Reversible inhibition of mammalian tubulin assembly in vitro and effects in Saccharomyces cerevisiae D61.M by mitomycin C

Gaulden reported a novel and unexpected mitomycin C (MMC) effect, namely a pronounced retardation of very late prophase and loss of chromosome orientation in neuroblasts of the grasshopper Chortophaga viridifasciate. Because this effect may be due to interactions of MMC with non-DNA targets, MMC was tested for its interaction with porcine brain tubulin assembly in vitro and for the induction of chromosomal malsegregation in the diploid yeast Saccharomyces cerevisiae strain D61.M. A reversible dose-dependent inhibition of tubulin assembly was observed. Since no biological activation system was present in the incubation mixture this inhibition seems to result from an interaction of unactivated MMC with the assembly process. The possible chemical activation of MMC by reduction with 1, 4-dithioerythritol (DTE) was investigated by omission of this compound during isolation and polymerization of tubulin. The absence of DTE resulted in a strong reduction of the net tubulin assembly. Also under these conditions MMC led to a dose-dependent inhibition of the assembly, indicating that the effect of MMC on tubulin assembly is independent of a reductive chemical modification. In S.cerevisiae D61.M, MMC did not induce chromosome loss, but induced other genetic events (possibly mutations, deletions or mitotic recombination) as was detected by an increase of the total number and of the frequency of cycloheximide-resistant colonies. This effect could be observed with and without the addition of rat liver S9 as an exogenous activation syste

Geometric K-Homology of Flat D-Branes

We use the Baum-Douglas construction of K-homology to explicitly describe various aspects of D-branes in Type II superstring theory in the absence of background supergravity form fields. We rigorously derive various stability criteria for states of D-branes and show how standard bound state constructions are naturally realized directly in terms of topological K-cycles. We formulate the mechanism of flux stabilization in terms of the K-homology of non-trivial fibre bundles. Along the way we derive a number of new mathematical results in topological K-homology of independent interest.Comment: 45 pages; v2: References added; v3: Some substantial revision and corrections, main results unchanged but presentation improved, references added; to be published in Communications in Mathematical Physic

Biomarkers in Natural Fish Populations Indicate Adverse Biological Effects of Offshore Oil Production

Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills.Samples from natural populations of haddock (Melanogrammus aeglefinus) and Atlantic cod (Gadus morhua) in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs) were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea.It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production

Reversible inhibition of mammalian tubulin assembly in vitro and effects in Saccharomyces cerevisiae D61.M by mitomycin C

Gaulden reported a novel and unexpected mitomycin C (MMC) effect, namely a pronounced retardation of very late prophase and loss of chromosome orientation in neuroblasts of the grasshopper Chortophaga viridifasciate. Because this effect may be due to interactions of MMC with non-DNA targets, MMC was tested for its interaction with porcine brain tubulin assembly in vitro and for the induction of chromosomal malsegregation in the diploid yeast Saccharomyces cerevisiae strain D61.M. A reversible dose-dependent inhibition of tubulin assembly was observed. Since no biological activation system was present in the incubation mixture this inhibition seems to result from an interaction of unactivated MMC with the assembly process. The possible chemical activation of MMC by reduction with 1, 4-dithioerythritol (DTE) was investigated by omission of this compound during isolation and polymerization of tubulin. The absence of DTE resulted in a strong reduction of the net tubulin assembly. Also under these conditions MMC led to a dose-dependent inhibition of the assembly, indicating that the effect of MMC on tubulin assembly is independent of a reductive chemical modification. In S.cerevisiae D61.M, MMC did not induce chromosome loss, but induced other genetic events (possibly mutations, deletions or mitotic recombination) as was detected by an increase of the total number and of the frequency of cycloheximide-resistant colonies. This effect could be observed with and without the addition of rat liver S9 as an exogenous activation syste