Decoding Complex Chemical Mixtures with a Physical Model of a Sensor Array

Combinatorial sensor arrays, such as the olfactory system, can detect a large number of analytes using a relatively small number of receptors. However, the complex pattern of receptor responses to even a single analyte, coupled with the non-linearity of responses to mixtures of analytes, makes quantitative prediction of compound concentrations in a mixture a challenging task. Here we develop a physical model that explicitly takes receptor-ligand interactions into account, and apply it to infer concentrations of highly related sugar nucleotides from the output of four engineered G-protein-coupled receptors. We also derive design principles that enable accurate mixture discrimination with cross-specific sensor arrays. The optimal sensor parameters exhibit relatively weak dependence on component concentrations, making a single designed array useful for analyzing a sizable range of mixtures. The maximum number of mixture components that can be successfully discriminated is twice the number of sensors in the array. Finally, antagonistic receptor responses, well-known to play an important role in natural olfactory systems, prove to be essential for the accurate prediction of component concentrations

Similarities between UDP-Glucose and Adenine Nucleotide Release in Yeast: Involvement of the Secretory Pathway

Extracellular UDP-glucose is a natural purinergic receptor agonist, but its mechanisms of cellular release remain unclear. We studied these mechanisms in Saccharomyces cerevisiae, a simple model organism that releases ATP, another purinergic agonist. Similar to ATP, UDP-glucose was released by S. cerevisiae at a rate that was linear over time. However, unlike ATP release, UDP-glucose release was not dependent on glucose stimulation. This discrepancy was resolved by demonstrating the apparent glucose stimulation of ATP release reflected glucose-dependent changes in the intracellular pattern of adenine nucleotides, with AMP release dominating in the absence of glucose. Indeed, total adenine nucleotide release, like UDP-glucose release, did not vary with glucose concentration over the short term. The genetic basis of UDP-glucose release was explored through analysis of deletion mutants, aided by development of a novel bioassay for UDP-glucose based on signaling through heterologously expressed human P2Y14 receptors. Using this assay, an elevated rate of UDP-glucose release was demonstrated in mutants lacking the putative Golgi nucleotide sugar transporter YMD8. An increased rate of UDP-glucose release in ymd8Δ was reduced by deletion of the YEA4 UDP-N-acetylglucosamine or the HUT1 UDP-galactose transporters, and overexpression of YEA4 or HUT1 increased the rate of UDP-glucose release. These findings suggest an exocytotic release mechanism similar to that of ATP, a conclusion supported by decreased rates of ATP, AMP, and UDP-glucose release in response to the secretory inhibitor Brefeldin A. These studies demonstrate the involvement of the secretory pathway in nucleotide and nucleotide sugar efflux in yeast and offer a powerful model system for further investigation

Assessment of natural resource conditions in and adjacent to Dry Tortugas National Park

This project characterized and assessed the condition of coastal water resources in the Dry Tortugas National Park (DRTO) located in the Florida Keys. The goal of the assessment was to: (1) identify the state of knowledge of natural resources that exist within the DRTO, (2) summarize the state of knowledge about natural and anthropogenic stressors and threats that affected these resources, and (3) describe strategies being implemented by DRTO managers to meet their resource management goals. The park, located in the Straits of Florida 113 km (70 miles) west of Key West, is relatively small (269 square kilometers) with seven small islands and extensive shallow water coral reefs. Significant natural resources within DRTO include coastal and oceanic waters, coral reefs, reef fisheries, seagrass beds, and sea turtle and bird nesting habitats. This report focuses on marine natural resources identified by DRTO resource managers and researchers as being vitally important to the Tortugas region and the wider South Florida ecosystem. Selected marine resources included physical resources (geology, oceanography, and water quality) and biological resources (coral reef and hardbottom benthic assemblages, seagrass and algal communities, reef fishes and macro invertebrates, and wildlife [sea turtles and sea-birds]). In the past few decades, some of these resources have deteriorated because of natural and anthropogenic factors that are local and global in scale. To meet mandated goals (Chapter 1), resource managers need information on: (1) the types and condition of natural and cultural resources that occur within the park and (2) the stressors and threats that can affect those resources. This report synthesizes and summarizes information on: (1) the status of marine natural resources occurring at DRTO; and (2) types of stressors and threats currently affecting those resources at the DRTO. Based on published information, the assessment suggests that marine resources at DRTO and its surrounding region are affected by several stressors, many of which act synergistically. Of the nine resource components assessed, one resource category – water quality – received an ecological condition ranking of "Good"; two components – the nonliving portion of coral reef and hardbottom and reef fishes – received a rating of "Caution"; and two components – the biotic components of coral reef and hardbottom substrates and sea turtles – received a rating of "Significant concern" (Table E-1). Seagrass and algal communities and seabirds were unrated for ecological condition because the available information was inadequate. The stressor category of tropical storms was the dominant and most prevalent stressor in the Tortugas region; it affected all of the resource components assessed in this report. Commercial and recreational fishing were also dominant stressors and affected 78% of the resource components assessed. The most stressed resource was the biotic component of coral reef and hardbottom resources, which was affected by 76% of the stressors. Water quality was the least affected; it was negatively affected by 12% of stressors. The systematic assessment of marine natural resources and stressors in the Tortugas region pointed to several gaps in the information. For example, of the nine marine resource components reviewed in this report, the living component of coral reefs and hardbottom resources had the best rated information with 25% of stressor categories rated "Good" for information richness. In contrast, the there was a paucity of information for seagrass and algal communities and sea birds resource components