A novel fluorescent sensor protein for detecting changes in airway surface liquid glucose concentration.

Both lung disease and elevation of blood glucose are associated with increased glucose concentration (from 0.4 to ~4.0 mM) in the airway surface liquid (ASL). This perturbation of ASL glucose makes the airway more susceptible to infection by respiratory pathogens. ASL is minute (~1 μl/cm(2)) and the measurement of glucose concentration in the small volume ASL is extremely difficult. Therefore, we sought to develop a fluorescent biosensor with sufficient sensitivity to determine glucose concentrations in ASL in situ. We coupled a range of environmentally sensitive fluorophores to mutated forms of a glucose/galactose-binding protein (GBP) including H152C and H152C/A213R and determined their equilibrium binding properties. Of these, GBP H152C/A213R-BADAN (Kd 0.86 ± 0.01 mM, Fmax/F0 3.6) was optimal for glucose sensing and in ASL increased fluorescence when basolateral glucose concentration was raised from 1 to 20 mM. Moreover, interpolation of the data showed that the glucose concentration in ASL was increased, with results similar to that using glucose oxidase analysis. The fluorescence of GBP H152C/A213R-BADAN in native ASL from human airway epithelial cultures in situ was significantly increased over time when basolateral glucose was increased from 5 to 20 mM. Overall our data indicate that this GBP is a useful tool to monitor glucose homoeostasis in the lung

Synthesis, Conformation and Antiproliferative Activity of Isothiazoloisoxazole 1,1-dioxides

Sixteen new isothiazoloisoxazole 1,1-dioxides, one new isothiazolotriazole and one new isothiazolopyrazole have been synthesised by using 1,3-dipolar cycloadditions to isothiazole 1,1-dioxides. One sub-set of these isothiazoloisoxazoles showed low μM activity against a human breast carcinoma cell line, whilst a second sub-set plus the isothiazolotriazole demonstrated an interesting restricted rotation of sterically hindered bridgehead substituents. A thiazete 1,1-dioxide produced from one of the isothiazole 1,1-dioxides underwent conversion into an unknown 1,2,3-oxathiazolin-2-oxide upon treatment with Lewis acids, but was inert towards 1,3-dipoles and cyclopropenones. Six supporting crystal structures are included

Ethnic-Racial Socialization in Early Childhood: The Implications of Color-Consciousness and Colorblindness for Prejudice Development

This chapter outlines how early childhood teachers can bring children into conversations surrounding race and racism by drawing on literature on how parents of color discuss these topics. Although educators’ practices surrounding race and racism remain largely unexplored, decades of developmental psychological research indicate that parents of color engage in ethnic-racial socialization practices that are beneficial for children (Hughes et al., 2006). The established dimensions of parental ethnic-racial socialization include (1) cultural socialization, or teaching children about their ethnic heritage and instilling ethnic pride; (2) preparation for bias, or teaching children about racism and preparing them to face discrimination; (3) promotion of mistrust, or warning children about the need to distance themselves from other racial groups; and (4) egalitarianism, or emphasizing the similarities between and equality of all races (Hughes et al. 2006). One consideration to take into account from a developmental perspective is that children’s level of cognitive development impacts how they interpret messages about race. This chapter draws a link between parental ethnic-racial socialization and extends this body of work to school settings, with a focus on teachers. The ideologies of colorblindness and color-consciousness are discussed throughout

Correlation Of Elector-Noise To Iron, Copper And Lead Release In A Changing Distribution System Water Quality Environment With And Without Inhibitors

This one year study focuses on the capability of corrosion inhibitors to mitigate the adverse effects of changing water quality in distribution systems that receive blended finished waters produced from ground, surface and saline sources. The inhibitors are Orthophosphate (OP), Blended ortho and polyphosphate (BOP), Zinc Orthophosphate (ZOP) and Silicate (Si). Data is collected from a large field facility, which includes 14 pilot distribution systems (PDS), 14 copper Corrosion Loops that contain one each Pb/Sn coupon, 14 Cradles that contain metal coupons that are used for chemical and biofilm studies, and 14 Nadles that are used to collect Electro-Noise (EN) data from Fe, Cu and Pb/Sn electrodes. The pipes used to construct the PDSs were taken from actual distribution systems. The samples collected from the PDSs, Corrosion Loops, Cradles and Nadles are paired by time and water quality. Metal release models using EN parameters are presented. The study began in February 2006 and data through October 17 2006 was used for model development. Corrosion monitoring is conducted by Linear Polarization, Electrochemical Impedance Spectroscopy and Electrochemical Noise techniques. The current data indicates that iron release correlates with localized corrosion (pitting) while copper release correlates with general corrosion. Inhibitors ranked by increasing effectiveness for reducing copper release are pH elevation, Si, ZOP, OP and BOP. © 2007 ASCE