Regulation of RNA Stability

This invention relates to the discovery that tristetraprolin (TTP) can promote the poly(A)RNase (PARN) mediated deadenylation of polyadenylated substrates containing AU-rich elements (AREs). As one aspect of the invention, the inventors have developed a cell free system that may be used for the purposes of assessing the effects of the various system components or their derivatives (i.e. AREs, PARN, or TTP) on the deadenylation process or the effects of various test agents on the deadenylation process.

A Tet-Regulated Mouse Model for Cataract

Cataract is the most common cause of blindness worldwide, with an estimated 25 million blind and 119 million visually impaired individuals worldwide. Over 20 million adults in the US alone are currently diagnosed with cataracts making this disease a major health concern. The incidence of cataract increases with age and a number of etiologic factors have been proposed in the pathogenesis of age-related cataract in humans including genetic factors, environmental factors and metabolic and biochemical changes in the crystalline lens.

Isolation of Hybridomas Producing Monoclonal Antibodies (MAbs) Inhibitory to Human CYP2J2

The National Institutes of Health announces three specific monoclonal antibodies that strongly inhibit and/or immunoblot the human cytochrome P450 2J2 (CYP2J2).

Cytochrome P450s catalyze the NADPH-dependent oxidation of arachidonic acid to various eicosanoids found in several species. The eicosanoids are biosynthesized in numerous tissues including pancreas, intestine, kidney, heart and lung where they are involved in many different biological activities.

Diagnostics and Therapeutics for Hydrocephalus

Congenital hydrocephalus is a significant public health problem, affecting approximately one in 500 live births in the United States. Congenital hydrocephalus has an adverse effect on developing brain and may persist as neurological defects in children and adults. Some of these defects may manifest as mental retardation, cerebral palsy, epilepsy and visual disabilities. Improved diagnostics are needed for assessing the risks of developing this debilitating disease.

Development of Reagents to Examine the Expression and Function of CYP2J Subfamily P450s

Cytochrome P450s catalyze the metabolism of a wide range of exogenous compounds, including drugs, industrial chemicals, environmental pollutants, and carcinogens. The 2C family of cytochrome P450 metabolizes an extensive number of drugs which include tolbutamide, S-Warfarin, mephenytoin, diazepam and taxol. The inventors cloned the cDNAs for several different CYP2J subfamily members including human CYP2J2, rat CYP2J3, mouse CYP2J5, mouse CYP2J6, and mouse CYP2J9. The recombinant proteins were expressed in insect cells.

Reducing Bloodstream Neutrophils as a Treatment for Lung Infection and Inflammation

During lung infection, bloodstream neutrophils (PMNs) responding to infection travel to the airspace lumen. Although successful arrival of microbicidal PMNs to the airspace is essential for host defense against inhaled pathogens, excessive accumulation of PMNs in the lung contributes to the pathogenesis of several prevalent lung disorders, including acute lung injury, bronchiectasis, and COPD. Unfortunately, there is no treatment for controlling PMN accumulation in the lung.

Therapeutic and Diagnostic Targets for Severe RSV Infection

Respiratory Syncytial Virus (RSV) infects nearly all children by their second birthday. RSV usually causes mild respiratory illness, however, a subset of patients experience severe infection that require hospitalization. Successful host defense against viral pathogens requires rapid recognition of the virus and activation of both innate and adaptive immunity. Toll-Like Receptors (TLRs) are responsible for mounting an innate immune response and genetic variations within TLRs modulate severity of infection.

Pyrophosphate Analog HIV-1 Reverse Transcriptase Inhibitors

The invention relates to compounds that inhibit HIV-1 DNA synthesis mediated by reverse transcriptase (RT). HIV-1 DNA synthesis by RT utilizes deoxynucleoside 5’-triphosphate (dNTP) as substrate and like many other enzymes, the reaction is reversible. Pyrophosphate analogs like imidodiphosphate strongly promote reverse reaction dNTP products containing the imidodiphosphate group instead of the naturally occurring pyrophosphate group. This imidodiphosphate-containing dNTP was found to be a potent inhibitor of the forward RT reaction.

TRPC Knockout (KO) Mice and Mice with a Floxed Allele of TRPC Ion Channel Genes

TRPCs (Canonical Transient Receptor Potential Channels) are a group of non-selective cation channels that allow sodium and calcium into cells. There are seven different genes in mice that code TRPCs. The in vivo roles played by TRPCs as a whole are poorly understood and very little is known about the in vivo roles played by individual TRPCs nor the role of these channels in specific tissues or cells.