Abstract: The present invention provides novel isolated polynucleotides and small molecule target polypeptides encoded by the polynucleotides. Antibodies that immunospecifically bind to a novel small molecule target polypeptide or any derivative, variant, mutant or fragment of that polypeptide, polynucleotide or antibody are disclosed, as are methods in which the small molecule target polypeptide, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states. More specifically, the present invention discloses methods of using recombinantly expressed and/or endogenously expressed proteins in various screening procedures for the purpose of identifying therapeutic antibodies and therapeutic small molecules associated with diseases. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

Abstract: The invention pertains to methods for detecting the presence or absence of a mutation associated with hypertrophic cardiomyopathy (HC). The methods include providing DNA which encodes a cardiac myosin binding protein and detecting the presence or absence of a mutation in the amplified product which is associated with HC. The invention further pertains to methods for diagnosing HC in a subject. These methods typically include obtaining a sample of DNA which encodes a cardiac myosin binding protein from a subject being tested for FHC and diagnosing the subject for FHC by detecting the presence or absence of a mutation in the sarcomeric thin filament protein which causes FHC as an indication of the disease. Other aspects of the invention include kits useful for diagnosing HC and methods for treating HC.

Abstract: The invention provides human G-protein coupled receptors (GCREC) and polynucleotides which identify and encode GCREC. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of GCREC.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of HsKif17, antibodies to HsKif17, methods of screening for HsKif17 modulators using biologically active HsKif17, and kits for screening for HsKif17 modulators.

Abstract: Tripartite molecular beacons (TMBs), are disclosed that are readily adaptable to high throughput applications. Each tripartite molecular beacon comprises three oligonucleotide components. The first oligonucleotide forms a hairpin stem and loop structure and the second and third oligonucleotides each comprise a sequence complementary to opposite strands of the hairpin stem. The second oligonucleotide has a fluorophore attached thereto and the third oligonucleotide has a quencher attached thereto.

Abstract: The present invention provides a system for generating nucleic acid molecules having a reduced ability to hybridize to form intermolecular and intramolecular base pairs between regions of substantial complementarity as compared with nucleic acid molecules having the same nucleotide sequence containing naturally-occurring nucleotides. Furthermore, nucleic acid molecules of the present invention are characterized by the ability to form intermolecular base pairs with other nucleic acid molecules of choice.

Abstract: The present invention describes the novel human G-protein coupled receptor (GPCR) BMSOTR and its encoding polynucleotide. Also described are expression vectors, host cells, antisense molecules, and antibodies associated with the BMSOTR polynucleotide and/or polypeptide of this invention. In addition, methods for treating, diagnosing, preventing, and screening for disorders or diseases associated with abnormal biological activity of BMSOTR are described, as are methods for screening for modulators, e.g., agonists or antagonists, of BMSOTR activity and/or function.

Abstract: The present invention provides mutant P-glycoprotein polypeptides that confer increased resistance to certain chemotherapeutic drugs relative to wild-type P-glycoprotein or P-glycoprotein having a glycine to valine substitution at position 185, and nucleic acid molecules encoding the same. The invention also provides antibodies that specifically bind mutant P-glycoproteins. The invention further provides methods for the diagnosis and treatment of conditions associated with P-glycoprotein-mediated multidrug resistance.

Abstract: A method of characterizing and/or identifying a binding complex, comprises the steps:

Abstract: The present invention provides methods for attenuating gene expression in a cell using gene-targeted double stranded RNA (dsRNA). The dsRNA contains a nucleotide sequence that hybridizes under physiologic conditions of the cell to the nucleotide sequence of at least a portion of the gene to be inhibited (the “target” gene).

Abstract: Biological material in a sample is reacted with a novel functionalized superparamagnetic Fe/Au nanoparticle that specifically binds to the biological material to produce a magnetic particle/biological material complex. The biological material is detected upon application of an electromagnetic magnetic field which separates the magnetic bound complex from other components of the reaction mixture.

Abstract: The invention relates generally to the discovery of specific nucleotide polymorphisms in the KCNE2 gene and the association of these polymorphisms with antibiotic-induced LQTS. Related composition screening systems and diagnostic and prognostic assays are provided.

Abstract: The invention provides human drug metabolizing enzymes (DME) and polynucleotides which identify and encode DME. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of DME.

Abstract: A novel process for producing data characterizing nucleic acids in proliferating cells using a tandem protocol for simultaneously building and expanding genomics/proteomics cancer databases while coordinating present and future genomic/proteomic individual patient assays by collecting a tissue sample including the proliferating cells; mechanically dividing the sample into cohesive multicellular particulates, and growing and analyzing the resulting cells. Sets of genetic data can be analyzed along with sets of corresponding clinical data, including phenotypic data, to form profiles that can aid in identifying proliferative diseases and in prognoses. A method for diagnosing proliferative diseases using the described assay methods is also provided. Lastly, a computing device is provided which permits searching analysis and entry of the genetic data, the corresponding clinical data and/or profiles.

Abstract: The present invention relates to a DNA polymerase immobilized by covalent bonding. More particularly, the present invention relates to an immobilized DNA polymerase whose activity is maximally preserved by masking the active site of the DNA polymerase and optimizing interaction of the masked molecule to the substrate material. In one embodiment, the average activity of the immobilized DNA polymerase is more than about 10% relative to that of the solution phase DNA polymerase. Further provided by the invention are methods and kits for performing polymerase chain reactions (PCR).

Abstract: The invention relates to the generation and characterization of archaeal DNA polymerase mutants with reduced base analog detection activity. The invention further provides for archaeal DNA polymerase mutants with reduced base analog detection activity containing additional mutations that modulate other DNA polymerase activities including DNA polymerization or 3′-5′ exonuclease activity. The invention also discloses methods and applications of DNA polymerases with reduced base analog detection activity.

Abstract: Methods of screening compounds which are oligomeric modulators of dehydrogenases such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and such oligomeric modulators. In one aspect, methods are presented for identifying an oligomeric modulator of a dehydrogenase, comprising contacting the dehydrogenase with a compound under conditions which allow oligomerization of the dehydrogenase to occur; and measuring the ability of the compound to modulate oligomerization of the dehydrogenase as an indication of whether the compound is an oligomeric modulator of the dehydrogenase. In another aspect, methods are presented for identifying an oligomeric modulator of GAPDH, comprising contacting GAPDH with a compound under conditions which allow oligomerization of GAPDH to occur; and measuring the ability of the compound to modulate oligomerization of GAPDH as an indication of whether the compound is an oligomeric modulator of GAPDH.

Abstract: The present invention disclosure provides methods and compositions for a universal tag assay wherein a universal detector having detection probes is incubated with tagged molecules having identifier tags corresponding to targets, and hybridization of an identifier tag to a complementary detection probe indicates the presence of the corresponding target in the material being assayed. In particular, the invention disclosure provides methods and compositions for detecting target nucleotide sequences in a sample by target-dependent manipulations that generate tagged molecules having identifier tags corresponding to target nucleotide sequence, where incubation of tagged molecules with a universal detector having detection probes permits hybridization of identifier tags to complementary detection probes, thereby indicating the presence of the target nucleotide sequence corresponding to each identifier tag.

Abstract: This invention relates to the purification, cloning and characterization of a novel gene, Gab2. In response to extracellular stimuli (e.g., cyokines, growth factors, hormones and antigens), Gab2 binds several signal relay molecules, including the protein-tyrosine phosphatase SHP-2 and phosphatidylinositol-3-OH kinase (PI-3K), which results in the initiation of multiple signaling cascades. Gab2 nucleic acid molecules, peptides, vectors, host cells, probes, antibodies, knockout and transgenic animals are provided. The invention also relates to methods of diagnosis, prevention and treatment of Gab2-mediated conditions such as allergic responses, neoplastic disorders and immune disorders.

Abstract: The present disclosure provides methods and compositions for conducting an assay to detect nucleic acid hybridization in the presence of oxygen. In particular, ruthenium complexes having a reduction potential that does not coincide with the reduction potential of molecular oxygen are disclosed and amperometric techniques for their use are described. In preferred embodiments, the ruthenium complex is ruthenium (III) pentaamine pyridine and the nucleic acid hybridization event that is detected is DNA hybridization. Further, techniques for enhancing detectable contrast between hybridized and unhybridized nucleic acids are disclosed. In particular, the use of elongated target strands as well as the use of uncharged probe strands are discussed.

Abstract: The present disclosure relates to the detection of somatic cell mutations, particularly as part of a method to screen for cancer or precancer. The disclosure includes techniques for extracting and isolating oligonucleotides from a patient and conducting hybridization assays. Preferred embodiments include a combination of the following steps: extracting a biological sample from a patient, purifying a nucleic acid from a biological sample, amplifying a nucleic acid, isolating a nucleic acid in single stranded form, cyclizing a nucleic acid, elongating a nucleic acid, controlling hybridization stringency, amplifying a nucleic acid on a chip, and detecting hybridization.

Abstract: The present invention provides polynucleotides encoding NF-kB-associated polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these NF-kB-associated polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

Abstract: The invention encompasses reagents comprising particles with at least one Raman dye and a specific binding members bound thereto and methods of using such reagents. The invention also encompasses reagents of a specific binding member and two or more different Raman dyes and methods for using such reagents. New types of particle probes having a specific binding member bound thereto are described. These reagents are used in a novel detection strategy that utilizes the catalytic properties of the Au nanoparticles to generate a silver coating that can behave as a surface-enhanced Raman scattering (SERS) promoter for the dye-labeled particles that have been captured by target and an underlying chip in microarray format.

Abstract: The present inventors conducted a similarity search of the amino acid sequence of known G protein-coupled receptor proteins in GenBank, and obtained a novel human GPCR gene “BG37”. cDNA containing the ORF of the gene was cloned and its nucleotide sequence was determined. Moreover, novel GPCR “BG37” genes from mouse and rat were isolated. Use of the novel GPCR of the present invention enables screening of ligands, compounds inhibiting the binding to a ligand, and candidate compounds of pharmaceuticals which can regulate signal transduction from the “BG37” receptor.

Abstract: The present invention relates to elongase genes, their polypeptides and their control regions, and the use of such genes, polypeptides and control regions in determining compositions for use in the treatment of disease. The identified compositions regulate the expression of the elongase genes or modulate the activity of their protein products. The nucleotide and amino acid sequences are taught for ELG4, ELG6 and ELG7. The control sequences and function are taught for ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7.

Abstract: A method of cloning mammalian genes encoding proteins which can function in microorganisms, particularly yeast, and can modify, complement, or suppress a genetic defect associated with an identifiable phenotypic alteration or characteristic in the microorganism. It further relates to mammalian genes cloned by the present method, as well as to products encoded by such genes and antibodies which can bind the encoded proteins. More specifically, the present invention relates to a method of cloning mammalian genes which encode products which modify, complement or suppress a genetic defect in a biochemical pathway in which cAMP participates or in a biochemical pathway which is controlled, directly or indirectly, by a RAS protein, to products (RNA, proteins) enocded by the mammalian genes cloned in this manner and to antibodies which can bind the encoded proteins.

Abstract: A method of constructing a gene function database comprising measuring the cell viabilities, against a plural number of drugs at various concentrations, of transformed eukaryotic cells overexpressing a plural number of function-known genes and parental cell line thereof, calculating the ratios of IC40 values of the transformed cells to the IC40 values of the parental cell line from the viabilities, calculating the logarithmic values of the ratios, and calculating the correlation coefficients among the known genes based on these logarithmic values; the database constructed by such a method; and a method of analyzing gene function of unknown genes is elucidated from the correlation coefficients of the function-unknown gene to each of the known genes in the database.

Abstract: The present invention relates to nucleic acids encoding modified polypeptides with fructosyl transferase activity, vectors containing this nucleic acid for the expression of the modified fructosyl transferase in prokaryotic or eukaryotic cells, host cells and/or transgenic plants containing these vectors, methods for producing high-molecular polyfructans with primarily &bgr;-1,2 bonds and a very low degree of branching, in particular inulin, method for producing fructooligosaccharides using the inulin produced according to the invention or using saccharose, as well as methods for producing difructose dianhydrides using the inulin produced according to the invention or using saccharose, as well as the use of the inulin produced according to the invention for the production of inulin ethers and inulin esters, and the use of fructooligosaccharides or hydrogenated fructooligosaccharides and difructose dianhydrides as a food additive, in particular as a dietetic food.

Abstract: Isolated nucleic acids comprising a lipocalin gene promoter region, isolated nucleic acids comprising a human lipocalin gene, isolated nucleic acids encoding a lipocalin polypeptide, isolated lipocalin polypeptides, and uses thereof. The disclosed lipocalin nucleic acids and polypeptides can be used to generate a mouse model of male infertility, for drug discovery screens, and for therapeutic treatment of fertility-related conditions.

Abstract: An assay comprising cells containing DNA which encodes a fusion protein containing a signal peptide fused and/or linked to a reporter gene protein for the identification of compounds which interfere with the process of cotranslational translocation and with the production of secreted or membrane protein.

Abstract: The invention provides human lipid-associated molecules (LIPAM) and polynucleotides which identify and encode LIPAM. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of LIPAM.

Abstract: The present invention provides a method for amplifying mRNA in ultramicroquantity by approximately 108 times which is possible to apply for generating a cDNA library, subtraction cloning, generating and analyzing a microarray, and analyzing a gene expression. After making mRNA of sample adsorbed to oligo (dT)-bound magnetic beads, a double-stranded cDNA is synthesized on magnetic beads, an antisense strand cDNA-bound magnetic beads are eliminated after adding a linker containing T7 promoter sequence at the 5′ end, by using a sense strand cDNA in supernatant as a template and using an oligo (dT) primer wherein a linker containing SP6 promoter sequence is added, a double-stranded cDNA is synthesized again, the cDNA mixture is amplified by PCR using a known sequence at a linker part of the both ends of said double-stranded cDNA as a primer. In addition, sense strand/antisense strand cRNA is synthesized by T7 or SP6 polymerase using said cDNA mixture.

Abstract: The present invention relates to a series of new chemical agents that demonstrate anti-tumor activity. More particularly, the present invention relates to molecules, referred to as “combi-molecules”, that combine two major mechanisms of anti-tumor action. A combi-molecule is capable of degrading to a ligand involved in cell signaling pathways and to an agent capable of damaging DNA. More specifically, the present invention relates to molecules capable of blocking epidermal growth factor receptor (EGFR) mediated signal transduction and capable of damaging DNA. The present invention also relates to a general method of synthesis of these combi-molecules.

Abstract: A soluble receptor that binds to IL-20 having two polypeptide subunits, IL-22R and IL-20RB. The two subunits are preferably linked together. In one embodiment one subunit is fused to the constant region of the light chain of an immunoglobulin, and the other subunit is fused to the constant region of the heavy chain of the immunoglobulin. The light chain and the heavy chain are connected via a disulfide bond.

Abstract: An improved method for detecting a target biomolecule directly in a polyacrylamide gel in which it has been separated from other substances. The improvement resides in, prior to binding the target to a probe and while the target biomolecule remains in the gel, (1) immersing the gel in a water miscible, aqueous extracting medium to shrink the gel by at least about ten percent and then (2) washing the gel with water to restore the gel to substantially its original size.

Abstract: The present invention provides DNA encoding a TADG-15 protein as well as a TADG-15 protein. Also provided is a vector capable of expressing the DNA of the present invention adapted for expression in a recombinant cell and regulatory elements necessary for expression of the DNA in the cell. The present invention further provides for methods of inhibiting TADG-15 expression and/or protease activity, methods of detecting TADG-15 mRNA and/or protein and methods of screening for TADG-15 inhibitors. Additionally, the present invention provides for cell-specific targeting via TADG-15 and methods of vaccinating an individual against TADG-15. The methods described are useful in the diagnosis, treatment and prevention of cancer, particularly breast and ovarian cancer.

Abstract: The present invention is directed to RNA interference using novel compositions and methods. In particular embodiments, the RNA compositions comprise double strand regions interrupted with non-complementary regions, wherein the RNA compositions are effective for regulation of transcription. In specific embodiments, transcription of a target nucleic acid sequence to which the RNA composition is directed is reduced or inhibited, such as by inducing destruction of at least one transcript. In other embodiments, multiple target nucleic acid sequences are targeted by the RNA compositions of the present invention.

Abstract: Methods for detecting the presence of foreign DNA in the DNA of a host organism are described. Probe libraries prepared from modified DNA, and from unmodified DNA, are competitively hybridized with reference DNA sequences cloned on solid phase supports, where the reference DNA sequences are characteristic of the foreign DNA. Probes containing the foreign DNA can thereby by isolated and/or identified.

Abstract: This invention relates to novel human polynucleotides and variants thereof, their encoded polypeptides and variants thereof, to genes corresponding to these polynucleotides and to proteins expressed by the genes. The invention also relates to diagnostic and therapeutic agents employing such novel human polynucleotides, their corresponding genes or gene products, e.g., these genes and proteins, including probes, antisense constructs, and antibodies.

Abstract: In one aspect of the invention, a method is provided for end-labeling RNA (total RNA, mRNA, cRNA or fragmented RNA). In one embodiment, T4 RNA ligase is used to attach a 3′-biotinylated AMP or CMP donor to an RNA acceptor molecule. In another embodiment, a pyrophosphate molecule 3′-AppN-3′-linker-biotin is used as donor molecule.

Abstract: The present invention involves the use of quantitative RT-PCR to identify AC133 as a marker. AC133 is prevalent on endothelial progenitor cells (EPCs), which are important cells in angiogenesis. Therefore, the invention is applied to ascertain the quantity of EPCs in a subject, and to diagnose and monitor angiogenesis, for example, in injured tissues and in cancer development and progression.

Abstract: Polypeptides whose expression is upregulated in liver tumor cells and cells from liver preneoplastic foci relative to expression in normal liver cells are disclosed as are polynucleotides that encode the polypeptides. In humans, the polynucleotide maps to a region of chromosome 15. The overexpression has also been confirmed in human liver, breast, colon and kidney cancer cell lines. It is believed that the polypeptides are overexpressed in tumor and preneoplastic cells in general.

Abstract: Methods for electronic perturbation of fluorescence, chemilluminescence and other emissive materials provide for molecular biological analysis.

Abstract: The present invention relates to a novel method for the detection and characterization of an unknown nucleic acid-binding protein from a biological sample. More particularly, the method of the instant invention includes the steps of forming nucleic acid-protein complexes, the subsequent selective degradation of of unbound nucleic acid molecules, the detection of nucleic acid-protein complexes, and finally, the characterization of the nucleic acid-binding protein. Additionally, compositions and methods are provided in the present invention for detecting and characterizing unknown nucleic acid-binding proteins from biological samples using immobilized nucleic acid molecules in reaction vessels having a multitude of wells.

Abstract: Compositions and methods are provided for identifying novel therapeutic agents for the treatment of breast cancer, bone marrow metastasis, pain, arthritis, aggressive behavior, depression, and certain hematopoietic disorders. Disclosed are promoters and 3′ regulatory regions of genes whose expression differs in malignant cells as compared with non-malignant cells. These include PPT-I, NK-2 and SP-R.

Abstract: The present invention relates to a new polypeptide and the gene coding therefore, gene being an evolutionarily conserved actin-binding protein, called STARS (striated muscle activator of Rho signalin), that is expressed specifically in cardiac and skeletal muscle cells and is upregulated in response to calcineurin signaling during cardiac hypertrophy. STARS is localized to the thin filament of the sarcomere and to actin stress fibers where it promotes actin bundling. STARS stimulates the transcriptional activity of serum response factor (SRF) through a mechanism that requires actin bundling and Rho kinase activation. STARS provides a mechanism for selectively enhancing the transcriptional activity of SRF in muscle cells and for linking changes in actin dynamics to gene transcription. Also disclosed are methods of using the gene and protein in drug screening and therapy, including, for example, use of the gene in gene therapy to treat cardiovascular disease.

Abstract: The present invention relates to methods and compositions for the diagnosis and treatment of metabolic disorders, including, but not limited to, obesity, diabetes, hyperlipidemia, overweight anorexia, or cachexia. The invention provides isolated nucleic acids molecules, designated 57242 nucleic acid molecules, which encode novel G protein-coupled receptor family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 57242 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 57242 gene has been introduced or disrupted. The invention still further provides isolated 57242 proteins, fusion proteins, antigenic peptides and anti-57242 antibodies. Methods of use of the provided 57242 compositions for screening, diagnostic and therapeutic methods in connection with metabolic disorders are also disclosed.

Abstract: The invention provides isolated nucleic acids molecules, designated 53010 nucleic acid molecules, which encode novel carboxylesterase members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 53010 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 53010 gene has been introduced or disrupted. The invention still further provides isolated 53010 proteins, fusion proteins, antigenic peptides and anti-53010 antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides a human carbamoyl phosphate synthase homolog (CPSH) and polynucleotides which identify and encode CPSH. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating or preventing disorders associated with expression of CPSH.

Abstract: The present invention provides a method for the in vitro selection of signaling aptamers comprising the steps of synthesizing a DNA pool, the DNA having a random insert of nucleotides of a specific skewed mole ratio; amplifying the DNA pool; transcribing an RNA pool from the amplified DNA using a fluorescently labeled nucleotide; applying the fluorescently labeled RNA pool to an affinity column to remove the high-affinity fluorescent RNA molecules from the fluorescently labeled RNA pool; obtaining a cDNA pool from the high-affinity fluorescent RNA molecules; repeating the amplification and selection steps on the fluorescent RNA molecules and cloning the fluorescent RNA molecules to yield signaling aptamers. Signaling aptamers comprising DNA molecules are also selected for. Also provided is a signaling aptamer that transduces the conformational change upon binding a ligand to a change in fluorescence intensity of the signaling aptamer.