A set of novel selenohydantoins were synthesized via a convenient and versatile approach involving the reaction of isoselenocyanates with various amines. We also revealed an unexpected Z→E isomerization of pyridin-2-yl-substituted selenohydantoins in the presence of Cu(2+) cations. The detailed mechanism of this transformation was suggested on the basis of quantum-chemical calculations, and the key role of Cu(2+) was elucidated.
View Article and Find Full Text PDFA rapid new approach to produce biologically relevant bisindoles, namely indolyltetrahydrocarbazoles and indolo[3,2-b]carbazoles, has been developed, based on the Ga(OTf)3 -catalyzed [3+3] cyclodimerization of indole-derived donor-acceptor cyclopropanes. Chemoselectivity of the process depends on the location of the three-membered ring at the indole core.
View Article and Find Full Text PDF(3 + 2)-Annulation of donor-acceptor cyclopropanes to alkynes induced by both Lewis and Brønsted acids has been developed. The reaction provides a rapid approach to functionalized indenes displaying intense visible emission (λmax = 430 nm, Φ = 0.28-0.
View Article and Find Full Text PDFA novel Lewis acid-catalyzed domino (3+2)-cyclodimerization of 2-arylcyclopropane-1,1-diesters and related stepwise cross-reaction of two different cyclopropanes were developed. These processes provide efficient and highly stereoselective access to polyoxygenated indanes and cyclopentannulated heteroarene derivatives, which display significant cytotoxicity against several lines of cancer cells (IC50 of 10(-6)-10(-5) M) while being non-toxic for normal cells.
View Article and Find Full Text PDFQuo vadis? The Lewis acid catalyzed reaction of (hetero)aryl-derived donor-acceptor cyclopropanes with alkenes can be selectively directed along a [3+2] annulation pathway (see scheme). This new process provides convenient and efficient access to indanes and other cyclopentannulated (hetero)arenes, among which polyoxygenated 1-arylindanes exhibit significant cytotoxicity against several cancer cell lines with an IC50 of 10(-6)-10(-5) M.
View Article and Find Full Text PDFTruncated and mutant forms ofp53 affect life span in Drosophila, nematodes and mice, however the role of wild-type p53 in aging remains unclear. Here conditional over-expression of both wild-type and mutant p53 transgenes indicated that, in adult flies, p53 limits life span in females but favors life span in males. In contrast, during larval development, moderate over-expression of p53 produced both male and female adults with increased life span.
View Article and Find Full Text PDFBackground: Several interventions increase lifespan in model organisms, including reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO transcription factor activation, dietary restriction, and superoxide dismutase (SOD) over-expression. One question is whether these manipulations function through different mechanisms, or whether they intersect on common processes affecting aging.
Results: A doxycycline-regulated system was used to over-express manganese-SOD (MnSOD) in adult Drosophila, yielding increases in mean and maximal lifespan of 20%.
Background: The sequencing of many genomes and tiling arrays consisting of millions of DNA segments spanning entire genomes have made high-resolution copy number analysis possible. Microarray-based comparative genomic hybridization (array CGH) has enabled the high-resolution detection of DNA copy number aberrations. While many of the methods and algorithms developed for the analysis microarrays have focused on expression analysis, the same technology can be used to detect genetic alterations, using for example standard commercial Affymetrix arrays.
View Article and Find Full Text PDFThe experimental spike-in studies of microarray hybridization conducted by Affymetrix demonstrate a nonlinear response of fluorescence intensity signal to target concentration. Several theoretical models have been put forward to explain these data. It was shown that the Langmuir adsorption isotherm recapitulates a general trend of signal response to concentration.
View Article and Find Full Text PDFThe application of microarray hybridization theory to Affymetrix GeneChip data has been a recent focus for data analysts. It has been shown that the hyperbolic Langmuir isotherm captures the shape of the signal response to concentration of Affymetrix GeneChips. We demonstrate that existing linear fit methods for extracting gene expression measures are not well adapted for the effect of saturation resulting from surface adsorption processes.
View Article and Find Full Text PDFAffymetrix GeneChips were used to measure RNA abundance for approximately 13,500 Drosophila genes in young, old, and 100% oxygen-stressed flies. Data were analyzed by using a recently developed background correction algorithm and a robust multichip model-based statistical analysis that dramatically increased the ability to identify changes in gene expression. Aging and oxidative stress responses shared the up-regulation of purine biosynthesis, heat shock protein, antioxidant, and innate immune response genes.
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