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This technology is directed to the discovery of specific microRNAs that target and downregulate enzymes within the cholesterol biosynthetic pathway and is currently being tested in vivo.

A method of detecting DNase I hypersensitive sites ((DHS) in a single cell or very small number of cells, including cells recovered from formalin-fixed paraffin-embedded (FFPE) tissue slides of patient samples. DHS has revealed a large number of potential regulatory elements for transcriptional regulation in various cell types. The application of DNase-Seq techniques to patient samples can elucidate pathophysiological mechanisms of gene function in a variety of diseases as well as provide potentially important diagnostic and prognostic information.

Aversive or anticraving medications are currently used to supplement behavioral treatment of alcohol dependence. However, there is a need for developing more effective medications than those available. Neuropeptide Y (NPY) is a neurotransmitter known for increasing appetite and possibly having a role in alcohol preference and dependence. This is likely to be mediated by activation of the post-synaptic NPY-Y1 receptor, but developing molecules suitable for human therapeutics that activate that receptor represents a major challenge.

Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice.

Smad4 knockout: Smad4 is essential for epiblast proliferation, egg cylinder formation and mesoderm induction in early embryogenesis.

FGFR4 knockout: Lung alveoli fail to develop normally in double mutant with FGFR4 and FGFR3 knockouts.

Floxed Bcl-x: Conditional knockout of pro-survival Bcl-x in primordial germ cells was used to study the balance between pro-apoptotic Bax during embryogenesis.

Vitamin D receptor (VDR) is a nuclear receptor that is activated by calcitriol, the active form of vitamin D. It is best known for regulating dietary calcium uptake necessary for bone growth, but it also affects cell proliferation and differentiation. Therefore, it was thought that treatment with calcitriol or its derivatives could be useful to treat the uncontrolled proliferation typical of cancer cells. However, this approach has been unsuccessful to date because it leads to toxic levels of calcium in the blood.

Gaucher disease, the most common lysosomal storage disease, is an inherited metabolic disorder in which harmful quantities of the lipid glucocerebroside accumulate in the spleen, liver, lungs, bone marrow and in rare cases in the brain, due to a deficiency of the enzyme glucocerebrosidase (Gba) that catalyses the first step in the biodegradation of glucocerebrosides. Type 1 Gaucher disease is the most common and is distinguished from the other forms of the disease, types 2 and 3, by the lack of neurologic involvement.

Diabetes affects over 120 million people worldwide (16 million in the US) and is a major health problem with associated health costs estimated at almost $100 billion dollars. Type 2 diabetes affects as many as 10% of the population of the Western World (with 15 million patients in the US alone) and arises from a heterogeneous etiology, with secondary effects from environmental influences. Risk factors for type 2 diabetes include obesity, high blood pressure, high triglycerides and age.