Abstract: The present invention relates to previously unknown disease associations between various genes, loci and biomarkers and essential hypertension. The detection of these biomarkers provides novel in vitro methods and test kits which can be used as an aid when making risk assessment, molecular diagnosis or prognosis of HT or a HT related condition. The disclosed methods and test kits do not require interaction with the body of a subject during the biomarker detection. Instead the methods and test kits are for in vitro use (e.g. in a clinical laboratory) and typically biological samples for the biomarker analyses using a method or a test kit of this invention have been collected earlier in a different place. In addition the biomarkers provide methods and systems for identifying novel agents for preventing, treating and/or reducing risk of HT or a HT related condition. The HT associated genes can be used to develop novel therapies for prevention and/or treatment of essential hypertension.

Abstract: Disclosed herein are nucleic acid molecules isolated from coffee (Coffea spp.) comprising sequences that encodes various sucrose metabolizing enzymes, along with their encoded proteins. Specifically, sucrose synthase, sucrose phosphate synthase and sucrose phosphatase enzymes and their encoding polynucleotides from coffee are disclosed. Also disclosed are methods for using these polynucleotides for gene regulation and manipulation of the sugar profile of coffee plants, to influence flavor, aroma, and other features of coffee beans.

Abstract: The present invention relates to a method for the treatment of depression comprising administering a therapeutically effective amount of gaboxadol to a patient, wherein the level of one or more inflammatory markers in said patient is increased or abnormal. The present invention also relates to a method for the treatment of stress-mediated depression comprising administering a therapeutically effective amount of gaboxadol to a patient, wherein the level of one or more inflammatory markers is increased or abnormal in said patient. The present invention also relates to a method for the treatment of depression or the amelioration of one or more depressive symptoms comprising administering a therapeutically effective amount of gaboxadol to a patient, wherein the clinical presentation of one or more symptoms of depression are the physiological effect of a general medical condition.

Abstract: The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL-4 induced processes associated therewith, methods and kits for identifying such compounds that utilize a CLLD8 protein as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vitro and ex vivo contexts.

Abstract: The present invention provides assays for detecting ADP, GDP and inorganic phosphate. These assays can be used directly to detect the presence of ADP, GDP and inorganic phosphate or can be used as part of a number of methods for identifying candidate agents that bind to a target protein or serve as modulators of the biological activity of a target protein.

Abstract: Described herein are methods which identify candidate agents as binding to a protein or as a modulator of the binding characteristics or biological activity of a protein. Generally, the methods involve the use of ADP or phosphate. The assays can be used in a high throughput system to obviate the cumbersome steps of using gels or radioactive materials.

Abstract: A method of detecting an etching end-point includes the steps of: forming a mask on a pattern area of an etching object; forming an etching indicator on an etching area of the etching object, which is not covered by the mask; etching the etching object using the mask; and evaluating the size of a remaining object covered by the mask using the etching indicator.

Abstract: The present invention relates to a method for quickly determining cAMP content or an adenylate cyclase activity in a biological sample containing non-cyclic adenine nucleotides without the use of radioactive agents. Particularly, the present invention provides a method of determining cAMP content or an adenylate cyclase activity in a biological sample containing non-cyclic adenine nucleotides selected from the group consisting of cAMP produced by endogenous adenylate cyclase, and AMP, ATP, ADP and a mixture thereof, which comprises (1) combining a biological sample with effective amounts of apyrase, adenosine deaminase and alkaline phosphatase to enzymatically remove non-cyclic adenine nucleotides other than cAMP, and glucose-6-phosphate in the sample; (2) enzymatically converting cAMP into AMP; (3) determining an amount of AMP without the use of radioactive agents, and a kit to carry out the method.

Abstract: This invention has as its object a method for detecting catalytic activity of a sample, characterized in that it comprises: the incubation of a substrate (S) with the sample that may have the catalytic activity that it is desired to detect, the addition of a reagent (X) that can react either with a chemical group of unconsumed substrate (S) or with a chemical group of product (P) that is formed after an incubation period with the sample, the addition of a developer (R) that can react with reagent (X), and the detection of the transformation of developer (R).

Abstract: Described herein are methods which identify candidate agents as binding to a protein or as a modulator of the binding characteristics or biological activity of a protein. Generally, the methods involve the use of ADP or phosphate. The assays can be used in a high throughput system to obviate the cumbersome steps of using gels or radioactive materials.

Abstract: A reagent for measuring an alanine aminotransferase activity comprising L-alanine, 2-oxoglutaric acid, lactate dehydrogenase, and reduced nicotinamide adenine dinucleotide, characterized by further comprising a substance having an activity of inhibiting lactate dehydrogenase activity is disclosed. Further, a method for measuring an alanine aminotransferase activity, characterized by bringing a sample to be analyzed, which may contain alanine aminotransferase, into contact with L-alanine, 2-oxoglutaric acid, lactate dehydrogenase, reduced nicotinamide adenine dinucleotide, and a substance having an activity of inhibiting a lactate dehydrogenase activity is disclosed. According to the reagent and method, an increase in the reagent blank reaction, i.e., an increase in the initial absorbance, can be suppressed.

Abstract: The present invention relates to nucleotide sequences of coryneform bacteria, coding for proteins involved in the bio-synthesis of L-serine and to methods for the isolation thereof. The invention further relates to an improved method for the production of L-serine. In addition, the present invention relates to the use of L-serine in the food, animal feed and/or pharmaceutical industries or in human medicine.

Abstract: The instant methods and compositions represent an advance in controlling drug resistance in microbes. AcrAB-like efflux pumps have been found to control resistance to drugs, even in highly resistant microbes. Accordingly, methods of treating infection, methods of screening for inhibitors of AcrAB-like efflux pumps, and methods of enhancing antimicrobial activity of drugs are provided. Pharmaceutical composition comprising an inhibitor of an AcrAB-like efflux pump and an antimicrobial agent are also provided.

Abstract: A microbe-specific medium for detection of vancomycin-resistant Enterococci in a test sample within 24 hours and preferably within 18 hours. The testing medium provides a selective growth medium for vancomycin-resistant Enterococci and includes specific nutrient indicators which only the target microbe can significantly metabolize and use for growth. The nutrient indicator contain a nutrient moiety and a detectable moiety linked together by a covalent bond. The nutrient indicators produce detectable signals only if the nutrient indicators are hydrolyzed by the Enterococci specific enzymes including ?-glucosidase and pyrrolidonyl arylamidase.

Abstract: A novel gene defining a novel human UDP-GlcNAc: Gal/Gl cNAc? 1-3GalNAc ??1, 6GlcNAc-transferase, termed C2/4GnT, with unique enzymatic properties is disclosed. The enzymatic activity of C2/4GnT is shown to be distinct from that of previously identified enzymes of this gene family. The invention discloses isolated DNA molecules and DNA constructs encoding C2/4GnT and derivatives thereof by way of amino acid deletion, substitution or insertion exhibiting C2/4GnT activity, as well as cloning and expression vectors including such DNA, cells transfected with the vectors, and recombinant methods for providing C2/4GnT. The enzyme C2/4GnT and C2/4GnT-active derivatives thereof are disclosed, in particular soluble derivatives comprising the catalytically active domain of C2/4GnT.

Abstract: The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL-4 induced processes associated therewith, methods and kits for identifying such compounds that utilize a CLLD8 protein as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vitro and ex vivo contexts.

Abstract: Methods, products and kits are provided for attaching agents to a body tissue surface via microparticles using endogenous or exogenous transglutaminase. The microparticles have surface available transglutaminase substrate reactive groups. In an embodiment, the groups are part of a polymer containing at least two contiguous linked lysines or at least three contiguous linked glutamines.

Abstract: Methods, products, compositions and kits are provided for attaching agents to tissue with a linking molecule in the presence of transglutaminase. The linking molecule and/or agent is a substrate of transglutaminase. The agent can be a nonprotein or an enzyme such as cholinesterase or phosphodiesterase. The transglutaminase may be exogenously added or be endogenous in tissue. In specific embodiments, the agent is not a transglutaminase substrate and the linking molecule is a substrate for transglutaminase containing at least two contiguous linked glutamines or at least three contiguous linked lysines, and may be a polymer. A conjugate of the agent and the linking molecule may be applied to tissue, and in the presence of transglutaminase covalently bonded to the tissue via the linking molecule.

Abstract: Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

Abstract: Disclosed is a process for obtaining an enzyme having a specified enzyme activity derived from a heterogeneous DNA population by screening, for the specified enzyme activity, a library of clones containing DNA from the heterogeneous DNA population which have been exposed to directed mutagenesis towards production of the specified enzyme activity. Also disclosed is a process for obtaining an enzyme having a specified enzyme activity by screening, for the specified enzyme activity, a library of clones containing DNA from a pool of DNA populations which have been exposed to directed mutagenesis in an attempt to produce in the library of clones DNA encoding an enzyme having one or more desired characteristics which can be the same or different from the specified enzyme activity.

Abstract: The present invention relates to a method for quickly determining cAMP content or an adenylate cyclase activity in a biological sample containing non-cyclic adenine nucleotides without the use of radioactive agents. Particularly, the present invention provides a method of determining cAMP content or an adenylate cyclase activity in a biological sample containing non-cyclic adenine nucleotides selected from the group consisting of cAMP produced by endogenous adenylate cyclase, and AMP, ATP, ADP and a mixture thereof, which comprises (1) combining a biological sample with effective amounts of apyrase, adenosine deaminase and alkaline phosphatase to enzymatically remove non-cyclic adenine nucleotides other than cAMP, and glucose-6-phosphate in the sample; (2) enzymatically converting cAMP into AMP; (3) determining an amount of AMP without the use of radioactive agents, and a kit to carry out the method.

Abstract: Amounts of components in a specimen can be analyzed with excellent quantitativity. The analysis includes: measuring an amount of a component to be analyzed in a specimen; measuring an amount of a standard component present originally and homeostatically in the specimen other than the component to be analyzed; determining the amount of the specimen from the amount of the standard component thus measured and a known concentration of the standard component in the specimen; and determining a concentration of the component to be analyzed in the specimen from the amount of the specimen thus determined and the amount of the component to be analyzed thus measured. The quantitative analysis of the present invention allows a component to be analyzed to be measured with high quantitativity as shown in FIG. 1.

Abstract: The invention relates to a method and to a diagnostic agent for detecting hemostasis disturbances, wherein, as a consequence of blood platelet aggregation, clot formation and/or clot dissolution, substances are brought to a distance from each other which permits or prevents an interaction, in particular an energy transfer, between the substances, and the extent of the interaction is measured.

Abstract: Described herein are methods which identify candidate agents as binding to a protein or as a modulator of the binding characteristics or biological activity of a protein. Generally, the methods involve the use of ADP or phosphate. The assays can be used in a high throughput system to obviate the cumbersome steps of using gels or radioactive materials.

Abstract: A method and compound for detecting and identifying and/or quantifying a deaminase enzymatic activity of a microorganism, according to which an inoculum suspected of containing a microorganism with a deaminase activity is brought into contact with a culture medium for microorganisms, wherein the culture medium comprises at least one detection agent for demonstrating, by forming a colored product with a revealing agent, a deaminase enzymatic activity; said detection agent being an L-amino acid of following general formula (I): in which R represents an organic radical containing a cyclic ring, said cyclic ring being substituted with 1 to 3 substituents that are identical or different and each of which limits the diffusion in the culture medium of the &agr;-keto acid produced by the deamination of the at least one detection agent, as compared to where each of said substituents is not present.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of HsKifC2, antibodies to HsKifC2, methods of screening for HsKifC2 modulators using biologically active HsKifC2, and kits for screening for HsKifC2 modulators.

Abstract: The instant methods and compositions represent an advance in controlling drug resistance in microbes. AcrAB-like efflux pumps have been found to control resistance to drugs, even in highly resistant microbes. Accordingly, methods of treating infection, methods of screening for inhibitors of AcrAB-like efflux pumps, and methods of enhancing antimicrobial activity of drugs are provided. Pharmaceutical composition comprising an inhibitor of an AcrAB-like efflux pump and an antimicrobial agent are also provided.

Abstract: A sensor for detecting an analyte enzyme includes at least one substrate compound and at least one indicator compound selected to produce a measurable change of state as a result of the interaction of the substrate and at least one target or analyte enzyme. Each of the indicator(s) and substrate(s) are incorporated within a single polymer.

Abstract: The present invention provides an enzymatic cycling assay for assessing the amount of homocysteine and/or cystathionine in a solution such as blood, blood, derivatives, or urine. The assay comprises the steps of contacting the solution containing homocysteine and/or cystathionine to form a reaction mixture, with CBS, or a derivative thereof, L-serine, and CBL, or a derivative thereof, for a time period sufficient to catalyze the cyclical conversion of homocysteine form to cystathionine and the reconversion of cystathionine to homocysteine with the production of pyruvate and ammonia; determining the amount of homocysteine and/or ammonia present in the reaction mixture; and determining the amount of homocysteine and/or cystathionine present in the solution based on the amount of pyruvate and/or ammonia formed. Expression vectors and isolation procedures for CBS, or derivatives thereof, and CBL, or derivatives thereof, are also provided as well as test kits for carrying out the assay.

Abstract: A two reagent-type kit for assaying GPT by acting GPT on L-alanine and &agr;-ketoglutarate in the presence of pyridoxal phosphate, converting the resulting pyruvate into lactate with L-lactate dehydrogenase (LDH) in the presence of reduced nicotinamide adenine dinucleotide (NADH) and measuring GPT based on a decrement of NADH, the GPT assay kit comprising a first reagent and a second reagent, one of which contains pyridoxal phosphate, L-alanine, &agr;-ketoglutarate, LDH and NADH and the other reagent contains no pyridoxal phosphate but contains L-alanine. The GPT assay kit is stable over a long period of time.

Abstract: Provided is a method of screening gene libraries derived from a mixed population of organisms for a bioactivity or biomolecule of interest. The mixed population of organisms can be a cultured population or an uncultured population from, for example, the environment. Also provided are methods of screening isolates or enriched populations of organisms, which isolates include a population that is spatially, temporally, or hierarchical, for example, of a particular species, genus, family, or class of organisms. Identified clones containing a biomolecule or bioactivity of interest can be further variegated or the DNA contained in the clone can be variegated to create novel biomolecules or bioactivities of interest.

Abstract: The present inventors have discovered that Asparagine Synthase is essential for fungal pathogenicity. Specifically, the inhibition of Asparagine Synthase gene expression in fungi results in no signs of successful infection or lesions. Thus, Asparagine Synthase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit Asparagine Synthase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Abstract: Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result the atoms proximal to the specificity ligand site can then be us ed as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

Abstract: The invention provides three human transferases (HUTRAN) and polynucleotides which identify and encode HUTRAN. 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 HUTRAN.

Abstract: Methods and compositions for the stabilization of aminotransferase activity of plasma or serum are provided. Such methods will be useful in the accurate determination of tests associated with liver toxicity.

Abstract: A microbe-specific medium for detection of vancomycin-resistant Enterococci in a test sample within 24 hours and preferably within 18 hours. The testing medium provides a selective growth medium for vancomycin-resistant Enterococci and includes specific nutrient indicators which only the target microbe can significantly metabolize and use for growth. The nutrient indicator contain a nutrient moiety and a detectable moiety linked together by a covalent bond. The nutrient indicators produce detectable signals only if the nutrient indicators are hydrolyzed by the Enterococci specific enzymes including &bgr;-glucosidase and pyrrolidonyl arylamidase.

Abstract: The present invention provides a method for measuring diacylglycerol acetyltransferase (DGAT) activity which utilizes a novel solvent system to reduce and/or eliminate the activities of related compounds.

Abstract: The invention relates to a method for determining homocysteine concentration in samples in which homocysteine is condensed using an enzyme cystathionine &bgr; sythase to form cystathionine. Pyruvate and/or ammonia are released from cystathionine by action of an enzyme, cystathionine &bgr; lyase, and homocysteine is regenerated. The release of pyruvate and/or ammonia can be correlated to the concentration of homocysteine present in the sample.

Abstract: Enzymatic methods to determine the concentration of pyridoxal 5′-phosphate (PLP) in biological fluids are described. The methods of the invention are useful to assess risk for cardiovascular disease. The assay can be a homogeneous assay using the ability of PLP to function as a co-enzyme for homocysteinase and related enzymes and measuring the products of the reaction preferably spectrophotometrically. The invention also includes improvements in sensitivity of assays for measuring hydrogen sulfide production by measuring fluorescence as opposed to absorbance of the oxidized product of H2S with N,N-dialkyl p-phenylene diamine.

Abstract: The invention features a method for evaluating PKC activity in vascular tissues. The invention also features methods for diagnosing cardiovascular and diabetes related disorders, and for identifying and evaluating treatments for cardiovascular or diabetes related disorders. Methods for identifying and evaluating treatments for aging are also included. The methods include measuring PKC activity in monocytes as a surrogate for PKC activity in other tissues.

Abstract: Described herein are methods which identify candidate agents as binding to a protein or as a modulator of the binding characteristics or biological activity of a protein. Generally, the methods involve the use of ADP or phosphate. The assays can be used in a high throughput system to obviate the cumbersome steps of using gels or radioactive materials.

Abstract: A method to assess the level of folate in a biological sample comprises.

Abstract: G protein-coupled receptor kinases (GRK) play an important role in phosphorylating and regulating the activity of G protein-coupled receptors. Complementary DNAs (cDNAs)that encode two novel members of the G protein-coupled receptor kinase (GRK) family are provided in the present invention. These cDNAs encode GRK5 (590 amino acids) and GRK6 (576 amino acids) which represent two new members of the GRK family that have distinct tissue distribution and substrate specificity. The availability of the cDNAs enables the generation of reagents to modulate the activity of endogenous kinases. These include dominant negative mutations and antisense oligonucleotides or stably transfected antisense constructs to block expression of the kinase to generate a cell with a reduced ability to desensitize to various agents. Expression of GRK5 and GRK6 also permits identification of specific inhibitors and activators of these two kinases.

Abstract: A microbe-specific medium for detection of vancomycin-resistant Enterococci in a test sample within 24 hours and preferably within 18 hours. The testing medium provides a selective growth medium for vancomycin-resistant Enterococci and includes specific nutrient indicators which only the target microbe can significantly metabolize and use for growth. The nutrient indicator contain a nutrient moiety and a detectable moiety linked together by a covalent bond. The nutrient indicators produce detectable signals only if the nutrient indicators are hydrolyzed by the Enterococci specific enzymes including &bgr;-glucosidase and pyrrolidonyl arylamidase.

Abstract: The instant methods and compositions represent an advance in controlling drug resistance in microbes. AcrAB-like efflux pumps have been found to control resistance to drugs, even in highly resistant microbes. Accordingly, methods of treating infection, methods of screening for inhibitors of AcrAB-like efflux pumps, and methods of enhancing antimicrobial activity of drugs are provided. Pharmaceutical composition comprising an inhibitor of an AcrAB-like efflux pump and an antimicrobial agent are also provided.

Abstract: A two reagent-type kit for assaying GPT by acting GPT on L-alanine and &agr;-ketoglutarate in the presence of pyridoxal phosphate, converting the resulting pyruvate into lactate with L-lactate dehydrogenase (LDH) in the presence of reduced nicotinamide adenine dinucleotide (NADH) and measuring GPT based on a decrement of NADH, the GPT assay kit comprising a first reagent and a second reagent, one of which contains pyridoxal phosphate, L-alanine, &agr;-ketoglutarate, LDH and NADH and the other reagent contains no pyridoxal phosphate but contains L-alanine. The GPT assay kit is stable over a long period of time.

Abstract: Amounts of components in a specimen can be analyzed with excellent quantitativity. The analysis includes: measuring an amount of a component to be analyzed in a specimen; measuring an amount of a standard component present originally and homeostatically in the specimen other than the component to be analyzed; determining the amount of the specimen from the amount of the standard component thus measured and a known concentration of the standard component in the specimen; and determining a concentration of the component to be analyzed in the specimen from the amount of the specimen thus determined and the amount of the component to be analyzed thus measured. The quantitative analysis of the present invention allows a component to be analyzed to be measured with high quantitativity as shown in FIG. 1.

Abstract: Methods for rapidly identifying drug candidates that bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

Abstract: The present invention provides a method for isotopically labeling a functional group possessed by an amino acid residue of a protein. The present invention also provides a protein whose functional group in an amino acid residue is isotopically labeled.

Abstract: The present invention relates to a method of screening for drug binding to serum proteins by: preparing at least two solutions each including a concentration of a serum protein and a concentration of a candidate drug, wherein the concentration of the candidate drug is different for each of the at least two solutions; exposing each of the at least two solutions to a light source; measuring fluorescent emission by the serum protein or a serum protein-candidate drug complex for each of the at least two solutions upon said exposing; and determining whether a change in fluorescence emission is measured for an increased concentration of the candidate drug, wherein the change in fluorescence emission indicates binding of the candidate drug to the serum protein. A kit useful for performing a fluorimetric screening of drug binding to serum proteins is also disclosed.