Discovering sequences with potential regulatory characteristics.

We developed a computational model to explore the hypothesis that regulatory instructions are context dependent and conveyed through specific 'codes' in human genomic DNA. We provide examples of correlation of computational predictions to reported mapped DNase I hypersensitive segments in the HOXA locus in human chromosome 7. The examples show that statistically significant 9-mers from promoter regions may occur in sequences near and upstream of transcription initiation sites, in intronic regions, and within intergenic regions.

A program toolkit for the analysis of regulatory regions of genes.

A major challenge in systems biology is to discover and reconstruct the cis-regulatory networks through which the expression of genes is controlled. Even though a variety of sequences have been shown to interact with the transcription factors that bind DNA, extensive work is needed to discover and classify regulatory "codes" and to elucidate the role played by the sequence context of genomic DNA in the regulation of genes. Databases of sequence elements extracted from regulatory regions may facilitate this process.

Exploring the characteristics of sequence elements in proximal promoters of human genes.

Central to reconstruction of cis-regulatory networks is identification and classification of naturally occurring transcription factor-binding sites according to the genes that they control. We have examined salient characteristics of 9-mers that occur in various orders and combinations in the proximal promoters of human genes. In evaluations of a dataset derived with respect to experimentally defined transcription initiation sites, in some cases we observed a clear correspondence of highly ranked 9-mers with protein-binding sites in genomic DNA.

Tomato extract inhibits human platelet aggregation in vitro without increasing basal cAMP levels.

Epidemiological data have reported an inverse relationship between the consumption of tomatoes and tomato products and the risk of cardiovascular disease. However, the mechanism(s) by which tomatoes may reduce cardiovascular disease risk are not yet known. The present study sought to determine whether an aqueous tomato fraction (tomato extract) could inhibit platelet aggregation in vitro.

Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects.

Background: Proanthocyanidins, the most abundant polyphenols in chocolate, are not depolymerized in the stomach and reach the small intestine intact, where they are hardly absorbed because of their high molecular weight. In vitro and in vivo studies using pure compounds as substrates suggest that proanthocyanidins and the related catechin monomers may be degraded into more bioavailable low-molecular-weight phenolic acids by the microflora in the colon.

Objective: The aim of the study was to estimate the amounts of phenolic acids formed by the microflora and excreted in the urine of human subjects after consumption of polyphenol-rich chocolate.

Stabilizing effect of ascorbic acid on flavan-3-ols and dimeric procyanidins from cocoa.

Cocoa flavanols and procyanidins have numerous biological activities. It is known that (-)-epicatechin, (+)-catechin, epicatechin-(4beta-8)-epicatechin (dimer B2), and epicatechin-(4beta-6)-epicatechin (dimer B5) are unstable at physiologic pH, degrading almost completely within several hours, whereas they are relatively stable at pH 5.0.

Cocoa procyanidins are stable during gastric transit in humans.

Background: Polyphenolic procyanidins are abundant flavonoid polymers in Western diets. In vitro biological activity has been reported for these compounds, but activity in vivo depends on the amount and chemical nature of the flavonoids reaching the gastrointestinal tract. Degradation of procyanidins under simulated gastric conditions at pH 2.

Influence of flavan-3-ols and procyanidins on UVC-mediated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in isolated DNA.

The flavan-3-ols (-)-epicatechin (epicatechin) and (+)-catechin (catechin) and their related oligomers (procyanidins) isolated from cocoa were assayed for their capacity to inhibit the UVC-mediated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo(8)dG) in calf thymus DNA. The above-mentioned compounds inhibited oxo(8)dG production in a concentration- and time-dependent manner. After 30 min of irradiation (30 kJ/m(2)), 0.

Procyanidin dimer B2 [epicatechin-(4beta-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa.

Background: Epidemiologic studies have linked flavonoid-rich foods with a reduced risk of cardiovascular mortality. Some cocoas are flavonoid-rich and contain the monomeric flavanols (-)-epicatechin and (+)-catechin and oligomeric procyanidins formed from these monomeric units. Both the monomers and the oligomers have shown potential in favorably influencing cardiovascular health in in vitro and preliminary clinical studies.

Inhibitory effects of cocoa flavanols and procyanidin oligomers on free radical-induced erythrocyte hemolysis.

Excessive peroxidation of biomembranes is thought to contribute to the initiation and progression of numerous degenerative diseases. The present study examined the inhibitory effects of a cocoa extract, individual cocoa flavanols (-)-epicatechin and (+)-catechin, and procyanidin oligomers (dimer to decamer) isolated from cocoa on rat erythrocyte hemolysis. In vitro, the flavanols and the procyanidin oligomers exhibited dose-dependent protection against 2,2'-azo-bis (2-amidinopropane) dihydrochloride (AAPH)-induced erythrocyte hemolysis between concentrations of 2.

Stability of the flavan-3-ols epicatechin and catechin and related dimeric procyanidins derived from cocoa.

Cocoa flavanols and procyanidins possess wide-ranging biological activities. The present study investigated the stability of the cocoa monomers, (-)-epicatechin and (+)-catechin, and the dimers, epicatechin-(4beta-8)-epicatechin (Dimer B2) and epicatechin-(4beta- 6)-epicatechin (Dimer B5), in simulated gastric and intestinal juice and at different pH values. The dimers were less stable than the monomers at both acidic and alkaline pH.

Flavanols and procyanidins of cocoa and chocolate inhibit growth and polyamine biosynthesis of human colonic cancer cells.

The effects of cocoa powder and extracts with different amounts of flavanols and related procyanidin oligomers were investigated on the growth of Caco-2 cells. Treatment of the cells with 50 microg/ml of procyanidin-enriched (PE) extracts caused a 70% growth inhibition with a blockade of the cell cycle at the G2/M phase. PE extracts caused a significant decrease of ornithine decarboxylase and S-adenosylmethionine decarboxylase activities, two key enzymes of polyamine biosynthesis.