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This technology includes adenosine receptor binding compounds which could potentially be used for development of more selective and safe treatment of cardiovascular, psychiatric and neurodegenerative disorders. Though adenosine has been extensively studied as a primary chemical scaffold for adenosine receptor agonists, very little structure activity data exist for C5' substitution. This technology presents novel rationally designed small molecule compounds capable of selective binding to adenosine receptor (subtypes A2a, A1, A2b and A3) and inducing effector-biased downstream signaling.

This technology includes a plasmid (designated pJH114) that encodes all five subunits of the E. coli Bam (barrel assembly machine) complex under the control of an inducible promoter to be used in the study of the Bam and screen for therapeutic small molecules. The Bam (barrel assembly machine) complex is a highly conserved heterooligomer that catalyzes the integration of membrane proteins that have a beta barrel structure into the outer membrane of Gram-negative bacteria. Research suggests that this complex is essential for the viability of most, if not all bacteria in this class.

This technology includes transgenic mice in which designer rat M3 muscarinic receptor mutants were expressed only in islet 13-cells (directed by rat insulin promoter II), were unable to bind acetylcholine (the endogenous ligand) but could be selectively activated by an otherwise pharmacologically inert compound (clozapine-N-oxide (CNO)). The R-q receptor contained a Y148C point mutation, which enabled CNO to selectively activate G proteins of the Gq/11 family. The R-5 receptor contained an A238G mutation, which enabled CNO to selectively activate G proteins of the G5 family.

This technology includes identification of the wild mouse microbiome as a method to increase resistance to lethal viral infection. We establish that the gut microbiome of barrier-raised C57BL/6 mice is dysbiotic compared to that of their outbred, wild-living progenitors, Mus musculus domesticus. We find that the multigenerational offspring of pregnant germfree C57BL/6 mice reconstituted with the gut microbiome of wild mice exhibit a less inflammatory response and increased survival following influenza A virus infection.

This technology includes a system for automatic artifact-free measurement and visualization of tissue strain by MRI at native resolution. The investigation of regional soft tissue mechanical strain can serve as a unique indicator for different related disorders. For example, measurement of myocardial tissue during contraction can help calculate, track, and assess cardiac stress. Currently, methods such as tagging MRI (tMRI) are used for imaging soft tissue deformation. Despite being well validated, methods such as tMRI suffer from low spatial and temporal resolution.

Purines such as adenosine and ATP have been shown to play a wide array of roles in biological systems such as inter alia, modulator of vasodilation and hypotension, muscle relaxant, central depressant, inhibitor of platelet aggregation, regulator of energy supply/demand, responder to oxygen availability, neurotransmitter and neuromodulator. All P1 and P2 receptor nucleoside ligands suffer from chemical instability that is caused by the labile glycosidic linkage in the sugar moiety of the nucleoside.

This technology includes MRS4322, which is an A3 agonist that is currently being evaluated for treatment of traumatic brain injury. Although its affinity in the receptor is in the micromolar range, it enters the brain in sufficient concentration to activate a protective CNS receptor, A3 adenosine receptor. Potential applications of such A3 agonists could also include neurodegenerative conditions.

The vast majority of people infected with Hepatitis C Virus (HCV) will have chronic infection. Over decades, this can lead to liver disease and liver cancer. In fact, HCV infection is the leading cause of liver transplants in the U.S. Several new drugs have recently come into the market that will likely change the HCV treatment paradigm. However, the effectiveness of these new drugs can vary depending on the HCV genotype. Thus, there is still the need for additional new therapeutics against HCV.

This technology includes a semi-automatic and affordable protein purification system that produces purified proteins with yields and purities comparable to an automatic protein purification system for less than 10% of its cost, which can be used for studying protein structure and function, as well as antibody purifications and drug screenings. Additionally, the new system is flexible and customizable for use with both custom-made and commercial pre-made resin columns with either gravity flow or low-pressure configurations.