Studies on the effects of the antitumor agent camptothecin and derivatives on DNA. Camptothecin potentiated cleavage of DNA by bleomycin in vitro

Addition of sodium camptothecin (2a, Fig. 1) in comparable low concentrations to the glycopeptide antitumor antibiotic bleomycin (BLM) leads to enhanced rates of single-strand scission of PM2-covalently closed circular DNA, whereas sodium camptothecin alone has no effect. A similar enhancement of DNA scission by sodium camptothecin is produced with the 1 : 1 bleomycin-iron complex alone or in conjunction with NADPH as an additional reductant. The interpretation that camptothecin may substitute for the reducing requirement of the antibiotic is supported by its oxidation at 37°C by the 1 : 1 bleomycin iron complex, by iron salts or more efficiently by hydrogen peroxide to the known hemiacetal (3, Fig. 1).Electrochemical studies of 2a, its analogues and selected model compounds established that the α-pyridone ring D is most susceptible to a one-electron reduction at a reversible potential of ?0.95 ± 0.01 V. The reduced camptothecin is a transient species readily capable of donating an electron. This process may by compatible with a coupled reduction of the sequestered Fe(III) in the glycopeptide antibiotic necessary for the expression of antibiotic and antitumor properties. The results may provide a mechanistic rationale for the observed potentiation of the antitumor activity of bleomycin by camptothecin in vivo.     

Heterogeneous genomic differentiation between walking-stick ecotypes: "isolation by adaptation" and multiple roles for divergent selection

Genetic differentiation can be highly variable across the genome. For example, loci under divergent selection and those tightly linked to them may exhibit elevated differentiation compared to neutral regions. These represent "outlier loci" whose differentiation exceeds neutral expectations. Adaptive divergence can also increase genome-wide differentiation by promoting general barriers to neutral gene flow, thereby facilitating genomic divergence via genetic drift. This latter process can yield a positive correlation between adaptive phenotypic divergence and neutral genetic differentiation (described here as "isolation-by-adaptation"). Here, we examine both these processes by combining an AFLP genome scan of two host plant ecotypes of Timema cristinae walking-sticks with existing data on adaptive phenotypic divergence and ecological speciation in these insects. We found that about 8% of loci are outliers in multiple population comparisons. Replicated comparisons between population-pairs using the same versus different host species revealed that 1-2% of loci are subject to host-related selection specifically. Locus-specific analyses revealed that up to 10% of putatively neutral (nonoutlier) AFLP loci exhibit significant isolation-by-adaptation. Our results suggest that selection may affect differentiation directly, via linkage, or by facilitating genetic drift. They thus illustrate the varied and sometimes nonintuitive contributions of selection to heterogeneous genomic differentiation.     

一个广告系统的脉冲控制

作者用脉冲微分系统的比较原理得到在同等效应下同一广告两次之间的最大时间间隔,并给出了数值例子。     

Frost resistance of winter rape leaves as related to the changes in water potential and growth capability

Differential thermal analysis indicated that the frost resistance of winter rape leaves ( Brassica napus L. var. oleifera L. cv. Gòrczanski), collected from plants grown in the cold (5/2°C), relies mainly on their ability to supercool to −9 to −11°C, i.e. consists in freezing avoidance. Initiation of ice formation in the cold-acclimated leaves resulted in the death of more than 50% of the cells as determined with a conductivity method. The development of freezing tolerance appeared to be an attribute of the second stage of plant hardening and was induced by the exposure of plants to a slightly subzero temperature (−5°C) for 18 h. Such a treatment brought about a sudden and persistent water potential decrease in the leaves, despite the fact that they had reabsorbed water from the medium prior to water potential measurements. Water potential changes were associated with a higher growth capability of the leaves as checked by determinations of disk area increments. It is suggested that the increased frost tolerance of the cold-grown winter rape leaves, subjected to subfreezing temperature, is related to the decreased water potential of the tissue caused by changes in turgor and/or in osmotic pressures of the cells.     

van't Hoff enthalpies without baselines

Analysis of thermal melting curves represents one important approach for evaluating protein stability and the consequences of amino acid substitution on protein structure. By use of the van't Hoff relationship, the differential melting curve can be robustly fit to only three parameters, two of which are the underlying physical constants of melting temperature (Tm) and van't Hoff enthalpy (deltaHvH). Calculated Tm and deltaHvH values are insensitive to the choice of pre- and post-transition baselines. Consequently, the method accurately computes Tm and deltaHvH for extremely truncated data sets, in the complete absence of baseline information, and for proteins with low melting temperatures, where the traditional direct approach routinely fails. Moreover, agreement between deltaHvH values obtained using points derived from pre- vs. post-transition data provide an independent method for detecting some classes of non-two-state transitions. Finally, fitting of the differential denaturation curve should prove useful for analysis of abbreviated data sets obtained from high throughput array analysis of protein stability.     

Insecticide susceptibility and resistance of Culex tritaeniorhynchus (Diptera: Culicidae) larvae collected from Gwangju,Republic of Korea

The susceptibility of Culex tritaeniorhynchus collected from Gwangju, Jeollabuk Province, Republic of Korea (ROK) to insecticides was evaluated under laboratory conditions using ten insecticides (7 pyrethroids and 3 organophosphates) that are currently applied by local public health centers in the ROK. Based on the values of median lethal concentration (LC₅₀), Cx. tritaeniorhynchus larvae were most susceptible to chlorpyrifos (0.006 ppm), fenitrothion (0.022 ppm), fenthion (0.035 ppm) and bifenthrin (0.038 ppm), and were least susceptible to esbiol (1.722 ppm). In comparative resistance tests, the resistance ratios (RRs) of seven insecticides were compared among each other using two strains of Cx. tritaeniorhynchus that were collected from the same locality during 1992 and 2010. Culex tritaeniorhynchus demonstrated significantly increased RRs to pyrethroids over time, while demonstrating decreased RRs among the organophosphates. Among the pyrethroids, permethrin had the highest RR values of 182.1‐ and 833.3‐fold differences, followed by etofenprox with RRs of 138.4‐ and 224.1‐fold differences in values of LC₅₀ and concentration that produced 90% mortality (LC₉₀), respectively. Culex tritaeniorhynchus strains demonstrated the least amount of change in susceptibility to the organophosphates, chlorpyrifos, fenitrothion and fenthion with 0.020‐, 0.019‐ and 0.001‐fold differences in resistance ratios (RRLC₅₀), respectively.