This invention provides bioluminescence resonance energy transfer (BRET) system that comprises four parts: 1) a bioluminescent protein that has luciferase activity; 2) an acceptor fluorophore that can accept the energy from the bioluminescent protein when they are associated, in the presence of the appropriate substrate; 3) a modulator that influences the proximity or the orientation of the bioluminescent protein and the fluorophore, and 4) an appropriate substrate to activate the luciferase activity of the bioluminescent protein. The components of this system interact to influence the spatial relationship between the bioluminescent protein and the fluorophore, that is demonstrated by the light emission from the system. The modulator can be a single entity, covalently attached to both the bioluminescent protein and the fluorophore, it can be two separate entities, each linked covalently to either the bioluminescent protein or the fluorophore, or an alternative configuration that falls within the scope of the invention. Thissystem can be used in both in vivo or in vitro assays to detect molecular changes in a wide variety of applications, and is amenable to automation. In particular, it is useful for assaying protein interactions, enzyme activities and the concentration of analytes or signaling molecules in cells or in solution.
A method of determining a local causal neighborhood of a target variable from a data set can include identifying variables of the data set as candidates of the local causal neighborhood using statistical characteristics, and including the identified variables within a candidate set. False positive variables can be removed from the candidate set according to further statistical characteristics applied to each variable of the candidate set. The remaining variables of the candidate set can be identified as the local causal neighborhood of the target variable.
Vanderbilt researchers have discovered specific morphogens that can promote differentiation of embryonic stem cells to cardiomyocytes. In addition when these morphogens are added to stem cells during differentiation a 10 to 20 fold increase is seen in cardiomyocyte formation. Thus addition of such morphogens may prove to be a valid therapy for cardiac repair and regeneration.
Vanderbilt researchers have identified compounds that selectively differentiate stem cells into cardiomyocytes by perturbing key pathways. Medicinal chemistry is currently underway to develop lead compounds that maybe used for the treatment of damaged cardiac muscle.
This is a genetically engineered mouse ES stem cell line marking cardiomyocytes with red fluorescent protein (RFP). These cells have been used in high-throughput screens by Vanderbilt researchers for pro-cardiogenic factors. In addition the construct used in this cell line could be used to mark the cardiac progeny of transplanted stem cells, generate stable human ES cell lines, or engineer iPS for cardiac lineage studies.
Dr. Piston's group has generated a variant of the enhanced cyan fluorescent protein (ECFP) that has improved brightness, more resistance to photo-bleaching and a fluorescence lifetime that is best fit by a single exponential.
Angioedema is a life-threatening and unpredictable side effect of angiotensin converting enzyme (ACE) inhibitors and ACE/Neutral endopeptidase (NEP) inhibitors, drugs aimed at reducing cardiovascular mortality associated with a variety of disease states. This technology permits the identification of individuals at risk for developing this angioedemic condition as a result of taking ACE inhibitors or NEP inhibitors. The patents and patent applications claim biological markers, diagnostic methods and kits.
A method of altering specificity of cyclooxygenase-inhibiting compounds that have a COOH moiety by changing the various COOH containing compounds, such as indomethacin, into ester derivatives or into secondary amide derivatives.
The c-Myc oncogene is bound by p19Arf, which inhibits c-Myc's ability to transform cells while augmenting apoptosis. This provides the basis for screening assays that examine the ability of various candidate substances to promote p19Arf interactions, or to substitute therefor.
The present invention is directed live, attenuated coronavirus vaccines. The vaccine comprises a viral genome encoding a p59 protein having at mutation at a specific tyrosine residue, and may include other attenuating mutations. Such viruses show reduced growth and pathogenicity in vivo.