Abstract: The invention relates generally to compositions of and methods for obtaining peroxisome proliferator-activated receptors. The invention relates as well to the DNA sequences encoding peroxisome proliferator-activated receptors, the recombinant vectors carrying those sequences, the recombinant host cells including either the sequences or vectors, and recombinant peroxisome proliferator-activated receptor polypeptides. By way of example, the invention discloses the cloning and functional expression of a peroxisome proliferator-activated receptor, designated PPAR-&ggr;, obtained from a human source. The invention includes as well, methods for using the isolated, recombinant peroxisome proliferator-activated receptor polypeptides in assays designed to select and improve substances capable of interacting with peroxisome proliferator-activated receptor polypeptides for use in diagnostic, drug design and therapeutic applications.

Abstract: A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis.

Abstract: In accordance with the present invention, there is provided an example of a novel class of nuclear receptor(s), termed the steroid X receptor (SXR). SXR is expressed almost exclusively in the liver, the primary site of xenobiotic and steroid catabolism. Unlike classical steroid receptors, SXR heterodimerizes with RXR and binds to directly repeated sequences related to the half-site, AGTTCA. SXR can activate transcription through response elements found in some steroid inducible P450 genes in response to a wide variety of natural and synthetic steroid hormones, including antagonists such as PCN—ideal properties for a “steroid sensing receptor” which mediates the physiological effect(s) of hormones. SXR represents the first new class of steroid receptors described since the identification of the mineralocorticoid receptor ten years ago.

Abstract: A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis.

Abstract: Remote, non-verbal interpersonal communication is facilitated between communication stations located remotely from each other. A first communication station registers proximity of a user thereto and communicates to a second communication station a signal indicative of the registered proximity. The first communication station also registers a physical gesture and communicates a signal indicative of the gesture to the second communication station. The second communication station, in turn, receives the signals and, in response thereto, produces a visual output indicative of proximity and of the gestural input.

Abstract: In accordance with the present invention, there is provided an example of a novel class of nuclear receptor(s), termed the steroid X receptor (SXR). SXR is expressed almost exclusively in the liver, the primary site of xenobiotic and steroid catabolism. Unlike classical steroid receptors, SXR heterodimerizes with RXR and binds to directly repeated sequences related to the half-site, AGTTCA. SXR can activate transcription through response elements found in some steroid inducible P450 genes in response to a wide variety of natural and synthetic steroid hormones, including antagonists such as PCN—ideal properties for a “steroid sensing receptor” which mediates the physiological effect(s) of hormones. SXR represents the first new class of steroid receptors described since the identification of the mineralocorticoid receptor ten years ago.

Abstract: In accordance with the present invention, there are provided new members of the steroid receptor superfamily of receptors, a representative member of which has been designated XOR-6. Invention receptors are responsive to hydroxy, mercapto or amino benzoates, and are expressed, for example, in Xenopus laevis embryos. XOR-6 is most closely, although distantly, related to the vitamin D3 receptor (VDR). The proteins are about 73% identical in amino acid sequence in the DNA-binding domains and about 42% identical in the ligand binding domain. Like VDR, XOR-6 has an extended D region between the DNA and ligand binding domains. Notably, the region amino-terminal to the XOR-6 DNA-binding domain is extremely acidic. This may influence its ability to activate target genes. XOR-6 is not restricted to Xenopus because southern blots show the presence of XOR-6-related sequences in a variety of other vertebrates. Indeed, a human genomic clone for an XOR-6 related gene has recently been isolated.

Abstract: A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis.

Abstract: In accordance with the present invention, there are provided new members of the steroid receptor superfamily of receptors, a representative member of which has been designated XOR-6. Invention receptors are responsive to hydroxy, mercapto or amino benzoates, and are expressed, for example, in Xenopus laevis embryos. XOR-6 is most closely, although distantly, related to the vitamin D3 receptor (VDR). The proteins are about 73% identical in amino acid sequence in the DNA-binding domains and about 42% identical in the ligand binding domain. Like VDR, XOR-6 has an extended D region between the DNA and ligand binding domains. Notably, the region amino-terminal to the XOR-6 DNA-binding domain is extremely acidic. This may influence its ability to activate target genes. XOR-6 is not restricted to Xenopus because southern blots show the presence of XOR-6-related sequences in a variety of other vertebrates. Indeed, a human genomic clone for an XOR-6 related gene has recently been isolated.

Abstract: Methods for screening cDNAs that express a product interacting with a target molecule. Individual cDNAs are pooled and the cDNA pools are expressed to obtain expression products, for example by coupled in vitro transcription/translation. The interaction of the products with the target molecule is then assayed, for example by scintillation proximity assay (SPA), to identify pools of interest. By selectively re-pooling the cDNAs and repeating the expression and assay steps, individual cDNAs of interest can be rapidly identified. This method is readily automated in a computer-controlled device for high throughput screening. The invention also provides methods of transfecting a cell with a cDNA identified by the screening method to confer a desired property to a cell or identifying cDNAs from a pool of cDNAs by transfection into cells to confer a desired property.

Abstract: The invention relates generally to compositions of and methods for obtaining peroxisome proliferator-activated receptors. The invention relates as well to the DNA sequences encoding peroxisome proliferator-activated receptors, the recombinant vectors carrying those sequences, the recombinant host cells including either the sequences or vectors, and recombinant peroxisome proliferator-activated receptor polypeptides. By way of example, the invention discloses the cloning and functional expression of a peroxisome proliferator-activated receptor, designated PPAR-&ggr;, obtained from a human source. The invention includes as well, methods for using the isolated, recombinant peroxisome proliferator-activated receptor polypeptides in assays designed to select and improve substances capable of interacting with peroxisome proliferator-activated receptor polypeptides for use in diagnostic, drug design and therapeutic applications.

Abstract: Novel peroxisome proliferator-activated receptor subunits designated PPAR.gamma. and PPAR.delta. are described. Nucleic acid sequences encoding the receptor subunits, expression vectors containing such sequences and host cells transformed with such vectors are also disclosed, as are heterodimeric PPAR receptors comprising at least one of the invention subunits, and methods for the expression of such novel receptors, and various uses therefor.