Down-Regulation of Serum/Glucocorticoid Regulated Kinase 1 in Colorectal Tumours Is Largely Independent of Promoter Hypermethylation

Background: We have previously shown that serum/glucocorticoid regulated kinase 1 (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal tissue. As hyper-methylation of promoter regions is a well-known mechanism of gene silencing in cancer, we tested whether the SGK1 promoter region was methylated in colonic tumour samples. Methodology/Principal Findings: We investigated the methylation profile of the two CpG islands present in the promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We further confirmed our findings in a panel of 10 normal and 10 tumour colonic tissue samples of human origin. We observed CpG methylation only in the smaller and more distal CpG island in the promoter region of SGK1 in both normal and tumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylation of the corresponding CpG. Conclusions/Significance: Our results show that even though partial methylation of the promoter region of SGK1 is present

Genomics of Parallel Experimental Evolution in Drosophila.

What are the genomic foundations of adaptation in sexual populations? We address this question using fitness-character and whole-genome sequence data from 30 Drosophila laboratory populations. These 30 populations are part of a nearly 40-year laboratory radiation featuring 3 selection regimes, each shared by 10 populations for up to 837 generations, with moderately large effective population sizes. Each of 3 sets of the 10 populations that shared a selection regime consists of 5 populations that have long been maintained under that selection regime, paired with 5 populations that had only recently been subjected to that selection regime. We find a high degree of evolutionary parallelism in fitness phenotypes when most-recent selection regimes are shared, as in previous studies from our laboratory. We also find genomic parallelism with respect to the frequencies of single-nucleotide polymorphisms, transposable elements, insertions, and structural variants, which was expected. Entirely unexpected was a high degree of parallelism for linkage disequilibrium. The evolutionary genetic changes among these sexual populations are rapid and genomically extensive. This pattern may be due to segregating functional genetic variation that is abundantly maintained genome-wide by selection, variation that responds immediately to changes of selection regime

Genomics of Parallel Experimental Evolution in Drosophila.

What are the genomic foundations of adaptation in sexual populations? We address this question using fitness-character and whole-genome sequence data from 30 Drosophila laboratory populations. These 30 populations are part of a nearly 40-year laboratory radiation featuring 3 selection regimes, each shared by 10 populations for up to 837 generations, with moderately large effective population sizes. Each of 3 sets of the 10 populations that shared a selection regime consists of 5 populations that have long been maintained under that selection regime, paired with 5 populations that had only recently been subjected to that selection regime. We find a high degree of evolutionary parallelism in fitness phenotypes when most-recent selection regimes are shared, as in previous studies from our laboratory. We also find genomic parallelism with respect to the frequencies of single-nucleotide polymorphisms, transposable elements, insertions, and structural variants, which was expected. Entirely unexpected was a high degree of parallelism for linkage disequilibrium. The evolutionary genetic changes among these sexual populations are rapid and genomically extensive. This pattern may be due to segregating functional genetic variation that is abundantly maintained genome-wide by selection, variation that responds immediately to changes of selection regime

Total (bio)synthesis: strategies of nature and of chemists

The biosynthetic pathways to a number of natural products have been reconstituted in vitro using purified enzymes. Many of these molecules have also been synthesized by organic chemists. Here we compare the strategies used by nature and by chemists to reveal the underlying logic and success of each total synthetic approach for some exemplary molecules with diverse biosynthetic origins