The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N 2 fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration.

Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage ( P ϭ 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers ( P ϭ 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups ( P Ͻ 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups. ( J. Clin. Invest. 1997. 99:725-731.)

Resveratrol in the fruits of bilberry (Vaccinium myrtillus L.), the lowbush "wild" blueberry (Vaccinium angustifolium Aiton), the rabbiteye blueberry (Vaccinium ashei Reade), and the highbush blueberry (Vaccinium corymbosum L.) were measured using a new assay based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS assay provided lower limits of detection than previous methods for resveratrol measurement, 90 fmol of trans-resveratrol injected on-column, and a linear standard curve spanning >3 orders of magnitude. The recoveries of resveratrol from blueberries spiked with 1.8, 3.6, or 36 ng/g were 91.5 +/- 4.5, 95.6 +/- 6.5, and 88.0 +/- 3.6%, respectively. trans-Resveratrol but not cis-resveratrol was detected in both blueberry and bilberry samples. The highest levels of trans-resvertatrol in these specimens were 140.0 +/- 29.9 pmol/g in highbush blueberries from Michigan and 71.0 +/- 15.0 pmol/g in bilberries from Poland. However, considerable regional variation was observed; highbush blueberries from British Columbia contained no detectable resveratrol. Because blueberries and bilberries are often consumed after cooking, the effect of baking on resveratrol content was investigated. After 18 min of heating at 190 degrees C, between 17 and 46% of the resveratrol had degraded in the various Vaccinium species. Therefore, the resveratrol content of baked or heat-processed blueberries or bilberries should be expected to be lower than in the raw fruit. Although blueberries and bilberries were found to contain resveratrol, the level of this chemoprotective compound in these fruits was <10% that reported for grapes. Furthermore, cooking or heat processing of these berries will contribute to the degradation of resveratrol.

Our results indicate that trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate are the most abundant metabolites of resveratrol. Virtually no unconjugated resveratrol was detected in urine or serum samples, which might have implications regarding the significance of in vitro studies that used only unconjugated resveratrol.

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INTRODUCTIONWe evaluated the relative contribution of CYP3A in the overall clearance of commonly used combined oral contraceptives (COCs) based on the results of clinical DDI studies in the literature and new drug applications (NDAs). The results revealed a limited role of CYP3A4 in the metabolism of COC components. Characterization of inhibition or induction spectrum of perpetrators on non-CYP3A pathways might also be crucial in predicting drug interaction potential of an investigational new drug with COCs.

BackgroundMost existing methods for phylogenetic analysis involve developing an evolutionary model and then using some type of computational algorithm to perform multiple sequence alignment. There are two problems with this approach: (1) different evolutionary models can lead to different results, and (2) the computation time required for multiple alignments makes it impossible to analyse the phylogeny of a whole genome. This motivates us to create a new approach to characterize genetic sequences.MethodologyTo each DNA sequence, we associate a natural vector based on the distributions of nucleotides. This produces a one-to-one correspondence between the DNA sequence and its natural vector. We define the distance between two DNA sequences to be the distance between their associated natural vectors. This creates a genome space with a biological distance which makes global comparison of genomes with same topology possible. We use our proposed method to analyze the genomes of the new influenza A (H1N1) virus, human rhinoviruses (HRV) and mammalian mitochondrial. The result shows that a triple-reassortant swine virus circulating in North America and the Eurasian swine virus belong to the lineage of the influenza A (H1N1) virus. For the HRV and mammalian mitochondrial genomes, the results coincide with biologists' analyses.ConclusionsOur approach provides a powerful new tool for analyzing and annotating genomes and their phylogenetic relationships. Whole or partial genomes can be handled more easily and more quickly than using multiple alignment methods. Once a genome space has been constructed, it can be stored in a database. There is no need to reconstruct the genome space for subsequent applications, whereas in multiple alignment methods, realignment is needed to add new sequences. Furthermore, one can make a global comparison of all genomes simultaneously, which no other existing method can achieve.

A novel clustering method is proposed to classify genes and genomes. For a given DNA sequence, a binary indicator sequence of each nucleotide is constructed, and Discrete Fourier Transform is applied on these four sequences to attain respective power spectra. Mathematical moments are built from these spectra, and multidimensional vectors of real numbers are constructed from these moments. Cluster analysis is then performed in order to determine the evolutionary relationship between DNA sequences. The novelty of this method is that sequences with different lengths can be compared easily via the use of power spectra and moments. Experimental results on various datasets show that the proposed method provides an efficient tool to classify genes and genomes. It not only gives comparable results but also is remarkably faster than other multiple sequence alignment and alignment-free methods.