Abstract: The present invention relates to novel compounds which are capable as acting as fluorescent sensors or which are precursors for these and for the use of these for the assay of biological processes such as posttranslational modifications of biological molecules such as phosphorylation, de-phosphorylation, proteolytic cleavage, phosphodiesterase mediated hydrolysis of cyclic nucleotides, methylation, acetylation of proteins peptides, DNA, lipids and the detection of biomolecule interactions (e.g., protein-protein interactions). A small molecule sensor is described which can associate to phosphorylated biological targets via metal ion—phosphate association. The association event can be monitored as fluorescence quench, sensitized emission, fluorescence polarization or a combination thereof.

Abstract: The present invention relates to methods of measuring the activity of a hydrolytic agent comprising contacting a biomolecule with a hydrolytic agent in the presence of a fluorescent dye under conditions that allow digestion of the biomolecule by the hydrolytic agent. The fluorescence of the dye is monitored over time and a change in fluorescence signifies digestion of the biomolecule by the hydrolytic agent. The biomolecule is preferably a protein, peptide or proteome but can also be a carbohydrate, oligonucleotide or lipid. Further methods relate to determining an end point for digestion of a biomolecule by a hydrolytic agent, and methods of monitoring digestion of a biomolecule by a hydrolytic agent. The monitoring can be performed on the reaction mixture in real time or via sampling. The invention also relates to kits for carrying out the method.

Abstract: The present invention relates to methods for treating or preventing lung cancer by administering a double-stranded molecule against one or more of EBI3, DLX5, NPTX1, CDKN3 or EF-I delta genes or compositions, vectors or cells containing such a double-stranded molecule. The present invention also features methods for diagnosing lung cancer, especially NSCLC or SCLC, using one or more over-expressed genes selected from among EBI3, DLX5, NPTX1, CDKN3 and/or EF-I delta. Also disclosed are methods of identifying compounds for treating and preventing lung cancer, using as an index their effect on the over-expression of one or more of EBI3, DLX5, CDKN3 and/or EF-I delta in the lung cancer, the cell proliferation function of one or more of EBI3, DLX5, NPTX1, CDKN3 and/or EF-I delta or the interaction between CDKN3 and VRS, EF-I beta, EF-I gamma and/or EF-I delta.

Abstract: The present invention concerns markers of resistance of HER2 expressing tumors to treatment with HER2 inhibitors, such as HER2 antibodies, including trastuzumab.

Abstract: Patients with ErbB2-overexpressing cancers can be given an ErbB2 targeting agent as a therapeutic regimen but not all patients are responsive. The present invention concerns the diagnostic, prognostic and therapeutic methods and compositions for evaluating potential efficacy of an ErbB2 targeting agent in an ErbB2-overexpressing cancers by evaluating PTEN expression, which is predictive of responsiveness or resistance to ErbB2 targeting agents such as trastuzumab. Low PTEN expression is predictive of a patient who will respond poorly to trastuzumab.

Abstract: Biomarkers and methods are disclosed for diagnosing the risk of a myocardial infarction in an individual by measuring the levels of a set of biomarkers in a sample from an individual. A risk score is calculated for the individual by weighting the measured levels of the biomarkers. The risk score then is used to identify whether the individual is likely to experience a myocardial infarction. In addition, kits are disclosed that include a set of reagents for specifically measuring biomarker levels in a sample from an individual.

Abstract: The invention relates to an assay for the identification of a compound having immunosuppressant activity, wherein a candidate compound is analyzed whether it blocks the Ca2+ flux in coronin 1 expressing cells and/or in coronin 1 negative cells. A candidate compound is identified as having immunosuppressant activity if it blocks the Ca2+ flux specifically in coronin 1 expressing cells. Further described are upstream assays wherein the impact of a candidate compound on coronin 1 trimerization is measured, and downstream assays wherein the impact of a candidate compound on diacyl glycerol (DAG) generation, phosphatidylinositol-4,5-biphosphate (PIP2) levels and/or inositol-1,4,5-triphosphate (InsP3) generation or on nuclear factor of activated T cells (NFAT) nuclear localization is determined.

Abstract: The present invention relates to a method for detecting a disease accompanied with neuropathy such as glaucoma, comprising measuring and/or detecting one or more of polypeptides shown in SEQ ID NOS: 1 to 15, mutants thereof, or fragments thereof in a biological sample from a subject, and also to a composition or kit for diagnosis of a disease accompanied with neuropathy such as glaucoma.

Abstract: A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a GPCR polypeptide, or fragment thereof, and measuring a compound-GPCR property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of GPCR expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

Abstract: A single molecule detection platform is disclosed. The single molecule detection platform comprises a light-transmissive substrate, a plurality of spherical particles and a thin film. The surface of the light-transmissive substrate is etched to form a plurality of cone-shaped structures. Each spherical particle is disposed on top of each cone-shaped structure. The sizes of the plurality of spherical particles are suitable to allow only a single protein to be attached to each spherical particle. The thin film is deposited on the surface of the plurality of cone-shaped structures and acts as a reflective layer of one-dimensional waveguide. The plurality of spherical particles is not covered by the thin film.

Abstract: A distinction method is provided to distinguish catch capacity where myosin, a protein that constitutes muscles, or filaments containing myosin bind to actin due to the contribution of twitchin that constitutes thick filaments along with myosin, while certain tension is sustained. The catch capacity is distinguished by using synthetic thick filaments containing myosin and twitchin, which are obtained from an extract of the muscles with a predetermined high salt buffer solution, and a soluble protein fraction obtained from the suspension of the above-mentioned muscles.

Abstract: The present invention relates to the use of a monophosphate ester of a phthalein compound as a substrate for Tartrate-Resistant Acid Phosphotase (TRAP). The substrate is used in assays for obtaining a measure of the amount of TRAP 5b in a sample of a subject, as an indication of the rate of bone resorption and therefore the likelihood of conditions such as osteoporosis. Also provided are kits comprising a monophosphate ester of a phthalein compound and optionally an antibody which binds total TRAP and methods.

Abstract: The present invention provides protein fragment complementation assays for drug discovery, in particular to identify compounds that activate or inhibit cellular pathways. Based on the selection of an interacting protein pair combined with an appropriate PCA reporter, the assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds. The interacting pair may be selected by cDNA library screening; by gene-by-gene interaction mapping; or by prior knowledge of a pathway. Fluorescent and luminescent assays can be constructed using the methods provided herein. The selection of suitable PCA reporters for high-throughput or high-content (high-context) assay formats is described for a diversity of reporters, with particular detail provided for examples of monomeric enzymes and fluorescent proteins.

Abstract: Human ALDO genes are identified as modulators of the IGF pathway, and thus are therapeutic targets for disorders associated with defective IGF function. Methods for identifying modulators of IGF, comprising screening for agents that modulate the activity of ALDO are provided.

Abstract: A method for differentiation of osteoarthritis from rheumatoid arthritis and non-disease conditions in a sample, comprising measuring in the sample the concentration of human cartilage intermediate layer protein 2 (CILP-2) in body fluids and more specifically, measuring in the sample the concentration of the N-terminal part of CILP-2 (2C1) or fragments thereof.

Abstract: A diagnostic device is provided for distinguishing between amniotic fluid and urine in female secretion. The device can be employed as a panty shield or can be adhered onto a panty shield or can be employed in a simple pad that is pressed against a substrate provided with female secretion.

Abstract: The present invention relates to a quantitative method for detecting yessotoxins in fishery products based on the activation the toxin produces on cellular phosphodiesterases and the therapeutic use of this activation. The cellular target of yessotoxin (YTX) and its analogs is the activation of phosphodiesterases (PDEs). The PDEs-YTX bond produces a measurable signal. The bond can be quantified by means of an affinity biosensor or by fluorescence. The biosensor detects biomolecular interactions and allows determining the presence of YTX due to its interaction with PDEs. The variations in the degradation rate of the fluorescent derivative anthraniloyl-cAMP are determined by means of plate fluorescence. The rate at which the PDEs degrade this molecule increases in the presence of YTX. YTX inhibits immunological activation of mastocytes in rats and induces a cytotoxic effect in human hepatocarcinoma cells, which implies two therapeutic uses of YTXs as an antiallergic and antitumor compound.

Abstract: The present invention relates to assays that can measure the activity of enzymes that catalyze phosphate modifications, such as kinases, phosphatases, cyclases and phosphodiesterases. The assays can also be used to identify and screen for substances that modulate the activity of kinases, phosphatases, cyclases and phosphodiesterases.

Abstract: This invention provides novel compositions and methods for the detection, and/or quantification, of the presence and/or activity of one or more kinases and/or phosphatases. In certain embodiments this invention a device for the detection of kinase and/or phosphatase activity where the device comprises a Raman active surface comprising features that enhance Raman scattering having attached thereto a plurality of kinase and/or phosphatase substrate molecules.

Abstract: The invention pertains generally to novel compositions and methods for constructing chemically sensitive ion channels. The compositions and methods include, for example, novel gramicidin A derivatives and their use in constructing novel ion channels for use as biosensors.

Abstract: The invention disclosed herein provides methods for the examination and/or quantification of biochemical pathways that are disregulated in pathologies such as cancer and to reagents and kits adapted for performing such methods.

Abstract: Methods are provided for ascertaining and measuring RPTP-? activity in response to insults such as UV irradiation and with respect to administration of a treatment and/or composition. Attenuation of EGFR activity by RPTP-? affects aspects of photoaging, including damage to the skin, suppression of the immune system, DNA damage, and connective tissue degradation. Intervention with respect to the effects of photoaging can include protection of RPTP-? from oxidation. The methods can be used for discovery of anti-aging treatments, adjuncts, or other preventative treatments, such as sunscreens.

Abstract: A reaction medium for detecting and/or identifying methicillin-resistant Staphylococcus aureus (MRSA) bacteria includes a chromogenic substrate, a first antibiotic that belongs to the cephalosporin family and a second antibiotic that belongs to the aminoglycoside family.

Abstract: The invention relates to methods to be used in the maturation of ovarian follicles and oocytes. More specifically, the invention concerns the use of inhibitors of the phosphatase PTEN, such as oxovanadate and peroxovanadate complexes, in methods for in vitro and in vivo maturation of follicles and oocytes.

Abstract: A fluorescent probe which is represented by the following formula (I): (wherein, R1 represents a monovalent substituent other than hydrogen atom, carboxy group, or sulfo group; R2 represents hydrogen atom, or a monovalent substituent; R3 and R4 each independently represents hydrogen atom or a halogen atom; and R5 represents a monovalent group which is cleaved by contact with a measuring object, provided that a combination of R1 and R2 is selected so that the oxidation potential of the benzene ring to which they bind makes (1) the compound represented by the formula (I) substantially no fluorescent before the cleavage, and (2) a compound after the cleavage, which is derived from the compound represented by the formula (I), substantially highly fluorescent after the cleavage).

Abstract: The ospF gene of Shigella flexneri encodes a phosphatase, which is a member of a new class of phosphatases. The OspF phosphatase inhibits the activity of several proteins either by direct protein modification or transcription downregulation. These proteins include MAP kinase, IL-8, CCL20, IL-12, AP1, CREB, RPA p32, and BCL2 related proteins. Methods for treating diseases using OspF phosphatase, methods for identifying agents that modulate OspF phosphatase's activity, methods for identifying agents that mimic OspF phosphatase's activity, and immunogenic compositions comprising OspF phosphatase are provided. A strain of Shigella flexneri containing an inactivated ospF gene is also provided.

Abstract: The present invention relates to a method for assessing in vitro the balance and the overall dynamics of a physiological condition, wherein a) a first biochemical marker representing a first biochemical process associated with the physiological condition is measured, b) a second biochemical marker representing a second biochemical process associated with the physiological condition is measured, c) the ratio of the results obtained in (a) and (b) is calculated, d) the square root of the sum of the squared results obtained in (a) and (b) is calculated and, e) wherein the ratio calculated in (c) is used to assess the balance of the physiological condition and wherein the square root calculated in (d) is used to assess the overall dynamics of the physiological condition.

Abstract: The invention provides a method for determining a degree of phosphorylation of a substrate, for example a peptide substrate, using a fluorescence probe that acts alone or with another material and has a lifetime that varies when in proximity to a phosphate, the method comprising: causing the fluorescence probe to fluoresce; measuring a time response of the fluorescence, and analysing the fluorescence time response to identify a fluorescence component having a lifetime associated with phosphorylated substrate and a fluorescence component having a lifetime associated with un-phosphorylated substrate.

Abstract: The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).

Abstract: The present invention relates to a method for quantifying protein tyrosine phosphatase (referred as PTP hereinafter) in biosamples, precisely a diagnostic method for disease by quantifying PTP using mass spectrometry and profiling of comparative PTP levels. By quantifying PTP in biosamples and profiling thereof according to the method of the present invention, disease can be diagnosed and diverse disease conditions and health conditions can be confirmed via profiling.

Abstract: One aspect of the present disclosure encompasses methods for determining a protein kinase or phosphatase activity in a biological sample, comprising: contacting in a reaction mix a first test sample and a fluorescently-labeled peptide substrate capable of being modified by a protein phosphatase or a protein kinase, contacting the reaction mix with a TiO2 matrix, thereby partitioning fluorescently-labeled phosphorylated peptide from fluorescently-labeled dephosphorylated peptide; and determining the fluorescence of the fluorescently-labeled dephosphorylated peptide, thereby determining a protein kinase or phosphatase activity.

Abstract: This invention is in the field of medical devices. Specifically, the present invention provides portable medical devices that allow real-time detection of analytes from a biological fluid. The methods and devices are particularly useful for providing point-of-care testing for a variety of medical applications. In particular, the medical device reduces interference with an optical signal which is indicative of the presence of an analyte in a bodily sample.

Abstract: A method of diagnosing Alzheimer's disease in a patient comprises determining whether the phosphorylation level of an indicator protein in cells of the patient after stimulus with an activator compound is abnormally elevated as compared to a basal phosphorylation level, the indicator protein being e.g. Erk1/2 and the activator compound being e.g. bradykinin.

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: The present invention provides novel JNK activating phosphatase polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, antibodies and methods for producing JNK activating phosphatase polypeptides. Also provided for are methods for the diagnosis and treatment of diseases associated with JNK activating phosphatase polypeptides.

Abstract: A coating material that is applied to a surface for absorbing a toxic chemical and that is removable from the surface by the use of mechanical force is disclosed. The coating material comprises one or more polymer coatings, one or more purified enzymes immobilized or entrapped in the polymer coating for protecting a surface from contamination by one or more toxic chemicals, one or more reporter indicators that are responsive to changes in pH in the presence of the toxic chemical for detecting and disclosing the location of said toxic chemical, and one or more buffers for establishing and/or maintaining the pH of the coating ranging from 5 to 10. Preferably, the reporter indicator is one or more pH-sensitive dyes or dye blends that change colors in the presence of the toxic chemical. A method for absorbing, detoxifying, detecting and disclosing of a toxic chemical is provided.

Abstract: A nanostructure comprising a core material of a nanometric size surrounded by an envelope of ordered fluid molecules is disclosed. The core material and the envelope of ordered fluid molecules are in a steady physical state. Also disclosed, a liquid composition comprising liquid and the nanostructure.

Abstract: A method of multiple protein biomarker detection, comprising providing at quantum dot-antibody conjugates that have an affinity for at least two different protein biomarkers; contacting the conjugates with a sample from a subject; allowing the proteins to bridge the antibodies, forming protein biomarker/quantum dot-antibody conjugate agglomerates; detecting the presence of the biomarkers by excitation of the agglomerates.

Abstract: The present invention relates to protein tyrosine phosphatase (PTP) and a method for preparing the same, precisely, a method for expressing PTP active domain with high activity and stability without help of a fusion protein, by using computer based protein structure prediction technique. PTP prepared by the method of the present invention can be effectively used as a protein for high efficiency drug screening for the development of a novel drug, as an antigen protein for the construction of a selective antibody and as a protein for the studies of PTP structure and functions.

Abstract: A plurality of markers determine the diagnosis of a mood disorder based on their expression in a sample such as blood. Subsets of biomarkers predict the diagnosis of high or low mood disorders. The biomarkers are identified using a convergent functional genomics approach based on animal and human data. Methods and compositions for clinical diagnosis of mood disorders are provided.

Abstract: Disclosed are compounds of the formula (I): wherein R3, R4, R5, R9, and R10 are selected from the group consisting of H and groups or atoms other than H, and R6 and R8 are halo or hydrogen; X1, X2, and X3 are independently O or S; provided that R9 and R10 are not simultaneously H, when all of X1, X2, and X3 are O; and of the formula (II) wherein R11-R14 are selected from the group consisting of H and groups or atoms other than H; X4-X9 are independently O or S; n and m are 0 or 1 but m and n cannot be 0 simultaneously; R15-R24 can be H or any substituent so long as the compound of formula II upon hydrolysis provides a fluorescent compound. These compounds are useful as substrates with high specificity for organophosphatase particularly human paraoxonase and bacterial organophosphorus hydrolase.

Abstract: A method of determining risk of heart failure in a mammal is provided comprising the steps of measuring in a biological sample obtained from a mammal the level of each of IL-6, MCP-1, IL-10, VEGF, and EGF biomarkers in the sample, wherein a positive result of at least three of said biomarkers is indicative of a risk of heart failure in the mammal.

Abstract: The present invention provides a method of identifying a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase, comprising: a) contacting the compound with a guanine nucleotide exchange factor and a GTPase and obtaining a baseline fluorescence measurement; b) contacting the guanine nucleotide exchange factor and the GTPase without the compound and obtaining a baseline fluorescence measurement; c) adding a fluorophore-conjugated GTP to the components of (a) and (b), respectively; d) obtaining fluorescence measurements of the respective components of (c) over time; e) subtracting the respective baseline fluorescence measurements of (a) and (b) from each fluorescence measurement of (d); and f) comparing the resulting fluorescence values of (e), wherein a decrease or increase in the rate of fluorescence change with the compound as compared with the rate of fluorescence change without the compound identifies a compound having the ability to modulate the guanine n

Abstract: Disclosed is a transgenic non-human animal with broad or cell type-specific ectopic expression of fra-2 that manifests itself in a fibrotic disease, methods for obtaining such animal and their use. Fra-2 transgenic animals, in particular mice, are useful as model systems for human fibrotic disease, e.g. lung scleroderma and pulmonary fibrosis. Cells obtained from the animal are useful for the analysis of fibrotic disease and for testing compounds useful in the therapy of fibrotic disease.

Abstract: Disclosed are methods for detecting thiol-containing nucleotide diphosphates. The methods utilize thiol-reactive fluorescent reagents.

Abstract: Compositions, methods, and kits for detecting and monitoring kinase, phosphatase and protein post-translational modification activity are described. The compositions typically include a peptide, a detectable moiety, and a protease cleavage site. Modification of a peptide by a kinase, phosphatase or other protein post-translational modification alters the proteolytic sensitivity of the peptide, resulting in a change of a detectable property of the composition. Panel assays for determining substrates or modulators of kinase, phosphatase or other protein post-translational modification activity are also described.

Abstract: The present invention provides diagnostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cell expresses certain sensitivity or resistance biomarkers, or genomic classifiers. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate this methodology are also provided.

Abstract: The invention concerns a medium for detecting, identifying and differentiating a microorganism strain in a liquid medium by contacting said liquid sample with a combination of chromogens substrates of enzymes expressed or not by the strain to be detected, the final coloration of the mixture being detectable in the wavelengths of the visible light.

Abstract: Disclosed is a method for cell storage on beads and subsequent utilisation of cryogenically stored cells in cellular assays.

Abstract: The invention relates to methylated proteins that control protein phosphorylation, particularly phosphoesterases, such as PP2A. It relates to screening methods for determining agents that affect methylation of these proteins and thus also modulate the level of phosphorylation of phosphoproteins. It relates as well to the agents and to compositions comprising the agents. In a particular aspect in this regard the invention relates to agents that alter PP2A methylation and that thereby affect phosphorylation of phosphoproteins that play an important role in health or disease, such as the tau protein which is implicated in the etiology of Alzheimer's Disease. The invention further relates to diagnostic methods based on protein methylation levels, to compositions comprising agents for affecting methylation of proteins and for controlling the phosphate complement of phosphoproteins.