A Genetic System in Yeast for Functional Identification of Human p53 Mutations

Mutations in the p53 gene are associated with 50% of all cancers and nearly 80% of the p53 mutations are missense changes. We have developed genetic assays based in yeast that can functionally categorize expressed p53 mutant proteins. The combined assays are referred to as the FIP53 system. Because human p53 cDNA can be conveniently cloned in yeast, the FIP53 system provides a rapid and sophisticated system for the functional analysis of p53 mutants. Four categories of mutations have already been identified.

Tristetraprolin (TTP) Plasmid Vectors for Human and Mouse TTP

Tristetraprolin (TTP) is involved in the physiological regulation of the secretion of at least two important cytokines, tumor necrosis factor alpha (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). TTP exerts its effects by directly binding to the mRNAs encoding these proteins and destabilizing them, resulting in less secretion. Conversely, TTP deficiency results in an excess of both cytokines, leading to a systemic inflammatory syndrome.

SIRT1 KO Human Cell Lines Generated by CRISPR/Cas9-mediated DNA Editing

SIRT1, a NAD+-dependent protein deacetylase, is the most conserved member of the sirtuins family. Through deacetylation of a number of protein substrates that are important transcription factors or co-factors, SIRT1 regulates many vital biological processes such as metabolism, cellular stress response, stem cell pluripotency, and development.

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.

Mice with a Floxed Allele of the alpha Subunit of the Heterotrimeric G Protein Go or Gi2

Heterotrimeric G proteins couple signals between GPCRs (G protein coupled receptors) and effectors such as adenylyl cyclase, phospholipase C and ion channels. Among the G proteins are Go and Gi2. Go is highly expressed in the brain and some endocrine tissues while Gi2 is widely expressed throughout the body. The ß?-subunits of Go interact with ion channels, and the a subunit has been shown to inhibit adenylyl cyclase. However a physiological role of the Gi2a has not been determined in a tissue specific manner.

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.

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.

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.

Methods of Screening for Risk of Cancer Using Human Lactoferrin DNA Probe or Primer

While normal breast ductal epithelium and neutrophilic granulocytes contain lactoferrin, their malignant counterparts frequently do not. The NIH announces primers or probes corresponding to the human lactoferrin gene, its promoter region, and its protein product, obtained from human breast tissue. The lactoferrin primer or probes can be used to screen for malignancy arising from tissues that normally secrete lactoferrin, or as a test to check the recovery of a patient from a malignancy.