Serum carbon isotope values change in adults in response to changes in sugar-sweetened beverage intake.

Serum carbon isotope values [13C-to-12C serum carbon isotope ratio (δ(13)C)], which reflect consumption of corn- and cane-based foods, differ between persons consuming high and low amounts of sugar-sweetened beverages (SSBs). In this study, we determined whether serum δ(13)C changes in response to change in SSB intake during an 18-mo behavioral intervention trial. Data were from a subset of 144 participants from the PREMIER trial, a completed behavioral intervention (Maryland, 1998-2004). SSB intake was assessed using 2 24-h dietary recall interviews. Blinded serum samples were assayed for δ(13)C by natural abundance stable isotope mass spectroscopy. Multiple linear regression models with generalized estimating equations and robust variance estimation were used. At baseline, mean SSB intake was 13.8 ± 14.2 fl oz/d, and mean δ(13)C serum value was -19.3 ± 0.6 units per mil (designated ‰). A reduction of 12 oz (355 mL)/d SSB (equivalent to 1 can of soda per day) was associated with 0.17‰ (95% CI: 0.08‰, 0.25‰ P < 0.0001) reduction in serum δ(13)C values over 18 mo (equivalent to a 1% reduction in δ(13)C from baseline). After adjusting for potential confounders, a reduction of 12 oz/d SSB (equivalent to 1 can of soda per day), over an 18-mo period, was associated with 0.12‰ (95% CI: 0.01‰, 0.22‰ P = 0.025) reduction in serum δ(13)C. These findings suggest that serum δ(13)C can be used as a measure of dietary changes in SSB intake

Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA

Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development

Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA

Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development.Molecular and Cellular Biolog