The invention is a device which permits the direct quantification of leachable organic constituents from within solid materials. It is expected that the device will be used in landfills and in other environments where measurements are central to the evaluation of the environmental compatibility of solid materials (e.g., sediments, soils, solidified waste forms) containing organic constituents that have the potential to degrade water resources of to be taken up by biota and the food chain. The invention is designed to simplify current difficulties in assessing leaching of organic constituents with low aqueous solubility.
A method of testing a candidate composition for PAI-1 inhibition activity is disclosed. The method includes the steps of obtaining a transgenic non-human warm blooded vertebrate animal having incorporated into its genome a PAI-1 gene encoding a biologically active PAI-1 polypeptide, the PAI-1 gene being present in the genome in a copy number effective to confer over-expression in the transgenic non-human animal of the PAI-1 polypeptide; administering the composition to the transgenic non-human animal; and observing the transgenic non-human animal for determination of a change in the transgenic non-human animal indicative of inhibition of the activity of PAI-1. A transgenic non-human animal useful in such a method is also disclosed, as is a PAI-1 transgene construct encoding a biologically active PAI-1 polypeptide useful for preparing the transgenic non-human animal.
The invention provides an isolated nucleic acid encoding the rat P450 2C11 arachidonic acid epoxygenase, or a human homologue thereof, having a mutation associated with salt induced hypertension. Also provided is an isolated cell line expressing the epoxygenase encoded by the mutated nucleic acid, and a non-human transgenic animal having a germ line insertion of the mutated nucleic acid. Also provided is a method of screening a compound for efficacy in treating salt induced hypertension comprising administering the compound to such a non-human transgenic animal, and detecting an improvement in the animal's hypertension. The invention also provides a method of screening a human subject for a genetic predisposition to salt induced hypertension comprising detecting a mutation in a human homologue of a rat P450 2C11 arachidonic acid epoxygenase gene which affects normal epoxygenase activity. Also provided is a method of treating salt induced hypertension in a human subject associated with a genetic mutation in a human homologue of the rat P450 2C11 arachidonic acid epoxygenase gene, comprising administering to the subject a functional metabolite, or analogue thereof, produced by the human homologue of the rat P450 2C11 arachidonic acid epoxygenase. Also provided is an isolated mutated rat P450 2C11 arachidonic acid epoxygenase, or a human homologue thereof, having a mutation associated with salt induced hypertension.
This technology facilitates the discovery and design of novel agents for either repelling or otherwise controlling insects that have important economic or medical significance. In particular, mosquitoes are responsible for transmitting a number of diseases, including malaria, West Nile, dengue and yellow fevers. The Zwiebel laboratory has identified human odorants and the protein receptors in mosquitoes that allow female mosquitoes to identify their hosts when they need blood to satisfy their reproductive needs. With funding from the Gates Foundation's Grand Challenge in Global Health initiative, the Zwiebel laboratory, along with collaborators at Yale, Wageningen University in the Netherlands, and researchers in Africa, developed biological and behavioral assays to screen and test numerous agents as potential repellants and attractants for the Anopholes gambiae mosquito. These methods have been applied to include agricultural pests, disease vectors and nuisance insects (important for many tourist-based economies).
Phosphodiesterase-5 (PDE5) is an enzyme which degrades cyclic guanosine monophosphate (cGMP) in smooth muscle cells. The common known drug Viagra is similar in molecular structure to cGMP and acts as a competitive binding agent of PDE5. Thus in the presence of Viagra unbound cGMP levels increase which results in smooth muscle relaxation or vasodilation leading to an increased inflow of blood. Vanderbilt researchers have developed a method for assaying compounds which bind PDEs. Not only will this method be useful in identify other PDE inhibitors but due to the high affinity of this system this method could be used to identify and isolate PDEs from various crude tissue fractions.