Über die Schreckreaktion bei Fischen und die Herkunft des Schreckstoffes

Ohne Zusammenfassung     

Acrocallosal syndrome in a child with de novo inverted tandem duplication of 12p11.2-p13.3.

Report on the child of normal unrelated parents presenting the typical features of acrocallosal syndrome (craniofacial dysmorphy, mental deficiency, convulsive disorder, agenesis of corpus callosum, preaxial polydactyly "hallux duplex" of both feet, and in addition diabetes insipidus) in which a mirror duplication of nearly the entire short arm of chromosome 12 was discovered. Since the symptomatology of trisomy and tetrasomy 12p shows some overlap with acrocallosal syndrome a common origin of the monogenic disorder and the chromosomal phenotypes is discussed.     

Systems Analysis of Bioenergetics and Growth of the Extreme Halophile Halobacterium salinarum

Halobacterium salinarum is a bioenergetically flexible, halophilic microorganism that can generate energy by respiration, photosynthesis, and the fermentation of arginine. In a previous study, using a genome-scale metabolic model, we have shown that the archaeon unexpectedly degrades essential amino acids under aerobic conditions, a behavior that can lead to the termination of growth earlier than necessary. Here, we further integratively investigate energy generation, nutrient utilization, and biomass production using an extended methodology that accounts for dynamically changing transport patterns, including those that arise from interactions among the supplied metabolites. Moreover, we widen the scope of our analysis to include phototrophic conditions to explore the interplay between different bioenergetic modes. Surprisingly, we found that cells also degrade essential amino acids even during phototropy, when energy should already be abundant. We also found that under both conditions considerable amounts of nutrients that were taken up were neither incorporated into the biomass nor used as respiratory substrates, implying the considerable production and accumulation of several metabolites in the medium. Some of these are likely the products of forms of overflow metabolism. In addition, our results also show that arginine fermentation, contrary to what is typically assumed, occurs simultaneously with respiration and photosynthesis and can contribute energy in levels that are comparable to the primary bioenergetic modes, if not more. These findings portray a picture that the organism takes an approach toward growth that favors the here and now, even at the cost of longer-term concerns. We believe that the seemingly “greedy” behavior exhibited actually consists of adaptations by the organism to its natural environments, where nutrients are not only irregularly available but may altogether be absent for extended periods that may span several years. Such a setting probably predisposed the cells to grow as much as possible when the conditions become favorable.     

Synthesis,cytotoxic activity,and DNA binding properties of antitumor cis-1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine cinnamoyl esters

Monocinnamoyl esters at position 2 of (±)-cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one and their acetyl derivatives at position 1 were prepared as stabilized analogues of the anticancer alkylating agent S23906-1. Monocinnamoyl esters at position 2 were slower DNA alkylators than the reference 2-monoacetate. Mixed esters bearing an acetyl ester group at position 1 and a cinnamoyl ester group at position 2 alkylated DNA slower than S23906-1. A strong correlation was observed between cytotoxicity and DNA alkylation kinetics, with slower alkylators displaying more potent antiproliferative activities. The most cytotoxic compounds proved to be significantly active in vivo against murine C-38 adenocarcinoma implanted in mice, but less potent than S23906-1.     

A modified and automated version of the 'Fluorimetric Detection of Alkaline DNA Unwinding' method to quantify formation and repair of DNA strand breaks

Background  

Formation and repair of DNA single-strand breaks are important parameters in the assessment of DNA damage and repair occurring in live cells. The 'Fluorimetric Detection of Alkaline DNA Unwinding (FADU)' method [Birnboim HC, Jevcak JJ. Cancer Res (1981) 41:1889–1892] is a sensitive procedure to quantify DNA strand breaks, yet it is very tedious to perform.     

Cancer chemotherapy: a SN-38 (7-ethyl-10-hydroxycamptothecin) glucuronide prodrug for treatment by a PMT (Prodrug MonoTherapy) strategy

A glucuronide-based prodrug of SN-38 (7-ethyl-10-hydroxycamptothecin) has been synthesized for use in a Prodrug MonoTherapy Strategy (PMT). Since this prodrug is significantly less cytotoxic than SN-38 itself and efficiently releases the drug in vitro in the presence of beta-D-glucuronidase, it can be considered as an appropriate candidate for cancer treatment by a PMT strategy.     

Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer

Considerable levels of testosterone and dihydrotestosterone (DHT) are found in prostate cancer (PCa) tissue after androgen deprivation therapy. Treatment of surviving cancer-initiating cells and the ability to metabolize steroids from precursors may be the keystones for the appearance of recurrent tumors. To study this hypothesis, we assessed the expression of several steroidogenic enzymes and stem cell markers in clinical PCa samples and cell cultures during androgen depletion. Gene expression profiles were determined by microarray or qRT-PCR. In addition, we measured cell viability and analyzed stem cell marker expression in DuCaP cells by immunocytochemistry. Seventy patient samples from different stages of PCa, and the PCa cell line DuCaP were included in this study. The androgen receptor (AR) and enzymes (AKR1C3, HSD17B2, HSD17B3, UGT2B15 and UGT2B17 ) that are involved in the metabolism of adrenal steroids were upregulated in castration resistant prostate cancer (CRPC). In vitro, some DuCaP cells survived androgen depletion, and eventually gave rise to a culture adapted to these conditions. During and after this transition, most of the steroidogenic enzymes were upregulated. These cells also are enriched with stem/progenitor cell markers cytokeratin 5 (CK5) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, putative stem/progenitor cell markers CK5, c-Kit, nestin, CD44, c-met, ALDH1A1, α2-integrin, CD133, ABCG2, CXCR4 and POU5F1 were upregulated in clinical CRPC. The upregulation of steroidogenic enzymes and stem cell markers in recurrent tumors suggests that cancer initiating cells can expand by adaptation to their T/DHT deprived environment. Therapies targeting the metabolism of adrenal steroids by the tumor may prove effective in preventing tumor regrowth.     

Regulation of the Ca-independent phospholipase A2 in liver mitochondria by changes in the energetic state

The effect of electron transport chain redox status on activity of the mitochondrial Ca²⁺-independent phospholipase A₂ (iPLA₂) has been examined. When oxidizing NAD-linked substrates, the enzyme is not active unless deenergization occurs. Uncoupler, rotenone, antimycin A, and cyanide are equally effective at upregulating the enzyme, while oligomycin is ineffective. Thenoyltrifluoroacetone causes deenergization and activates the enzyme, but only if succinate is the respiratory substrate. These findings show that the mitochondrial iPLA₂ responds to the energetic state overall, rather than to the redox status of individual electron transport chain complexes. With NAD-linked substrates, and using rotenone to deenergize, iPLA₂ activation can be reversed by adding succinate to reestablish a membrane potential. For this purpose, ascorbate plus N,N,N′N′-tetramethyl-phenylenediamine can be used instead of succinate and is equally effective. With succinate as substrate, the membrane potential can be reduced in a graded and stable fashion by adding increasing concentrations of malonate, which is a competitive inhibitor of succinate utilization. A partial and stable activation of the iPLA₂ accompanies partial deenergization. These findings suggest that in addition to the several functions that have been proposed, the mitochondrial iPLA₂ may help to coordinate local capillary blood flow with changing energy demands.     

Synthesis by a clonal line of rat glial cells of a protein unique to the nervous system

The synthesis of a protein unique to the nervous system, the “S100-protein,” has been studied in a clonal line of rat glial cells. It has been shown that these cells do not begin to accumulate “S100-protein” until the cultures enter a phase of density-dependent inhibition of cell proliferation. Further experiments indicate that the regulation of “S100-protein” accumulation resides at least in part in an interaction involving the cell surface.