Abstract: A display and method of preparing 7-transmembrane and other receptors for real-time kinetic analysis of binding interactions. The invention includes display on beads and in micelles for multi-well and flow cytometric analysis. The invention is useful for ligand discovery and drug action discovery, and G-protein response in particular.

Abstract: The present invention provides isolated highly active hedgehog proteins esterified with a fatty acid having from 14 to 20 carbon atoms at the N-terminal domain of the protein. The highly active hh proteins are particularly useful therapeutic agents for treating bone disorders and neurodegenerative diseases. Methods for obtaining the highly active modified hedgehog proteins are also provided.

Abstract: Four novel members of the EPH sub-family of receptor protein tyrosine kinases are disclosed. Nucleic acid sequences encoding receptor proteins, recombinant plasmids and host cells for expression, and methods of producing and using such receptors are also disclosed.

Abstract: The present invention includes the receptor protein 4-1BB and the cDNA gene encoding for receptor protein 4-1BB. The nucleotide sequence of the isolated cDNA is disclosed herein along with the deduced amino acid sequence. The 4-1BB protein and fragments and derivatives can be used: 1) as a probe to isolate ligands to receptor protein 4-1BB, 2) to stimulate proliferation of B-cell's expressing 4-1BB, or 3) to block 4-1BB ligand binding. A monoclonal antibody against 4-1BB was developed which specifically recognizes an epitope on the extracellular domain of receptor protein 4-1BB. The monoclonal antibody can be used enhance T-cell proliferation and activation by treating T-cells that have expressed receptor protein 4-1BB with the monoclonal antibody. The effectiveness of the treatment was enhanced when conducted in the presence of protein tyrosinase kinase. A fusion protein for detecting cell membrane ligands to receptor protein 4-1BB was developed.

Abstract: The present application is directed to the discovery that hedgehog gene products, and signal transduction pathways involving hedgehog, are involved in maturation of T lymphocytes. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, agonists, antagonists, or other molecules which regulate patched or smoothened signalling, and their uses as immunomodulatory agents.

Abstract: Isolated nucleic acid molecules, i.e., DNA or RNA encoding human neuronal nicotinic acetylcholine receptor alpha and beta subunits, mammalian and amphibian cells containing said DNA, methods for producing ? and ? subunits and recombinant (i.e., isolated or substantially pure) ? subunits and ? subunits are provided. In addition, cells expressing various multimeric combinations of subunits (i.e., ?1, ?2 ?3 ?4 ?5 ?6 and/or ?7 in combination with at least one of an ? and ? subunit are also provided. A recombinant, non-human cell line expressing the human ?7 subunit of nAChR is disclosed.

Abstract: Invertebrate and vertebrate patched genes are provided, including the mouse and human patched genes, as well as methods for isolation of related genes, where the genes may be of different species or in the same family. Having the ability to regulate the expression of the patched gene, allows for the elucidation of embryonic development, cellular regulation associated with signal transduction by the patched gene, the identification of agonist and antagonist to signal transduction, identification of ligands for binding to patched, isolation of the ligands, and assaying for levels of transcription and expression of the patched gene.

Abstract: The present application is directed to the discovery that hedgehog gene products are able to protect peripheral nerve cells under conditions which otherwise result in peripheral neuropathy. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, or other molecules which regulate patched or smoothened signalling, and their uses as protective agents against both acquired and hereditary neuropathies. As used herein, “peripheral neuropathy” refers to a disorder affecting a segment of the peripheral nervous system. For instance, the method of the present invention can be used as part of a treatment program in the management of neuropathies associated with systemic disease, e.g., viral infections, diabetes, inflamation; as well as genetically acquired (hereditary) neuropathies, e.g., Charcot-Marie-Tooth disease; and neuropathies caused by a toxic agent, e.g., a chemotherapeutic agent such as vincristine.

Abstract: The present invention relates to a novel human protein called Cytokine Receptor Common Gamma Chain Like, and isolated polynucleotides encoding this protein. Also provided are vectors, host cells, antibodies, and recombinant methods for producing this human protein. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to this novel human protein.

Abstract: Replacement of codons in DNA encoding the first three SCRs of LHR-A of CR1 with others encoding the predicted amino acids in the CR1-like sequence can give rise to chimeric genes which can be expressed to give active complement inhibitors with functional complement inhibitory, including anti-haemolytic activity. There is provided a soluble polypeptide comprising, in sequence, one to four short consensus repeats (SCR) selected from SCR 1, 2, 3 and 4 of long homologous repeat A (LHR-A) as the only structurally and functionally intact SCR domains of CR1 and including at least SCR3, in which one or more of the native amino acids are substituted with the following: Val 4, Asp 19, Scr 53, Lys 57, Ala 74, Asp 79, Arg 84, Pro 91, Asn 109, Lys 116, Val 119, Ala 132, Thr 137, Ile 139, Ser 140, Tyr 143, His 153, Leu 156, Arg 159, Lys 161, Lys 177, Gly 230, Ser 235, His 236.

Abstract: The invention relates to polypeptides which exert the biological activity of GABA B receptors, and to nucleic acids which encode these polypeptides, and in particular to their use for finding active compounds for crop protection.

Abstract: This invention relates to an isolated nucleic acid fragment encoding scorpion toxins that are Na-channel modifiers. The invention also relates to the construction of a chimeric gene encoding all or a substantial portion of the Na-channel modifier, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the Na-channel modifier in a transformed host cell.

Abstract: One aspect of the present application relates to a method for limiting damage to neuronal cells by ischemic or epoxic conditions, e.g., such as may be manifest by a reduction in brain infarct volume, by administering to an individual a hedgehog therapeutic or ptc therapeutic in an amount effective for reducing cerebral infarct volume.

Abstract: A method of screening for non-steroidal neuropsychiatric agents includes determining the ability of a candidate non-steroidal agent to selectively regulate or alter the central nervous system content and/or bioavailability of an endogenous neuroactive steroid. In particular, the method includes determining the ability of the agent to selectively regulate a rate-limiting step in the bio-control of the bioavailable amount of an endogenous neuroactive steroid, wherein the rate-limiting step may be either a step in biosynthesis of an endogenous neuroactive steroid, such as allopregnanolone, or a step in the biodegradation of such an endogenous neuroactive steroid. Alternatively, the method may include determining the ability of a candidate agent in selectively regulating the rate of reuptake of an endogenous neuroactive steroid by neurons or glial cells.

Abstract: The present invention provides an isolated DNA molecule that codes for a cell-surface binding protein in human monocytes and macrophages. In addition, an amino acid sequence derived from the nucleotide sequence is provided. The newly-identified cell-surface binding protein described herein is instrumental in the apoB-mediated cellular uptake of plasma chylomicrons and remnants and hypertriglyceridemic triglyceride-rich lipoproteins in an ApoE- and lipoprotein lipase- and heparin sulfate proteoglycan-independent pathway. The new human macrophage receptor has been cloned and uniquely, binds TGRLP via apolipoprotein B48, the marker of dietary TGRLP (apoB48R). This process rapidly converts macrophages and apoB48R-transfected Chinese hamster ovary cells in vitro into lipid-filled “foam cells,” hallmarks of atherosclerotic lesions. The apoB48R cDNA (3744 bp) encodes a novel protein with no known homologs. Its ˜3.8 kb mRNA is expressed primarily by reticuloendothelial cells.

Abstract: Methods are provided that are useful in assaying compounds for cognitive enhancing properties, anxiolytic properties, hypnotic properties, or antidepressant properties. These methods involve determining the in vitro efficacy and EC50 of the compounds at defined series of cloned GABAA subtype receptors composed of specific variants of &agr;,&bgr;, and &ggr; subunits in order to develop and an activity profile for each compound. Optionally, the binding affinities of the compounds at GABAA receptors are also determined. As an additional step the in vivo effects of the compounds may be tested in animal models.

Abstract: A method for identifying compounds that can be useful for producing analgesia is disclosed. In particular, the method involves providing preparation of a cell, that expresses an alpha1B adrenergic receptor, combining a test compound with the cell preparation, measuring the effect of the test compound on the alpha1B receptor activity, and evaluating the compound thus identified for analgesic activity.

Abstract: Matrices that support cell adhesion and growth are disclosed that deliver low heparin-binding affinity growth factor protein peptides in a controlled manner. These matrices comprise covalently or non-covalently bound heparin or heparin-like polymers, which serve to sequester the low heparin-binding affinity growth factor protein peptides within the matrix. The controlled release of some low heparin-binding affinity growth factor or peptides thereof occurs by degradation of some matrix component or dissociation of the low heparin-binding affinity growth factor protein peptides from the bound heparin. This differs from many controlled delivery devices in that release is not controlled solely by diffusion, and the rate of release may therefore be regulated by altering the rate of degradation of the matrix component or the amount of heparin bound within the matrix. The controlled release of such low heparin-binding affinity growth factor proteins such as NGF-&bgr;, NT-3 and BDNF, is demonstrated.

Abstract: The present invention is directed to isolated nucleic acid molecules encoding human platelet F11 receptors. Expression vectors and host cells comprising the nucleic acid molecules are also provided, as well as methods for increasing or decreasing the expression of the human platelet F11 receptor in host cells. The invention further provides a method of screening a substance for the ability of the substance to modify human platelet F11 receptor function, and a method for isolating other human platelet F11 receptor molecules. DNA oligomers capable of hybridizing to the nucleic acid molecule encoding the human platelet F11 receptor are provided, which can be used to detect human platelet F11 receptor in a sample.

Abstract: Transformed cells designed to express a recombinant human SMBP at an elevated level to the extent that its ligand-binding activity can be measured, and cellular membrane fractions thereof; recombinant human SMBPs isolated from the transformed cells or the cellular membrane fractions thereof; a screening system for human SMBP agonists/antagonists characterized by utilizing the transformed cells, the cellular membrane fractions thereof or the isolated recombinant human SMBPs; and human SMBP agonists or antagonists obtainable by the screening system, are provided by deleting the polythymidine sequence from the base sequence of the 3′-untranslated region.