Abstract: The present invention is related to the field of phospholipid detection. In particular, certain embodiments provide the detection of phosphatidic acid. For example, certain proteins are capable of binding phosphatidic acid and can be used as a diagnostic and/or research tool to identify and quantitate phosphatidic acid. Phosphatidic acid may be in or from cells and tissues isolated from plants, animals and humans. For example, a trigalactosyldiacylglycerol-2 (TGD2) protein may be fused with a fluorescent probe to monitor and measure phosphatidic acid in vitro as well as in vivo. In other embodiments, a trigalactosyldiacylglycerol-4 (TGD4) protein may be fused with a fluorescent probe to monitor and measure phosphatidic acid in vitro as well as in vivo. In additional embodiments, a fragment comprising either a truncated TGD2 or TGD4 phosphatidic acid binding region protein may be used to monitor or measure phosphatidic acid.

Abstract: The present invention generally relates to a nicotinamide adenine dinucleotide (NAD) biosynthesis system and methods of screening for NAD biosynthesis effectors. Among the various aspects of the present invention is the provision of an in vitro-reconstituted mammalian NAD biosynthesis system that can be used for the high-throughput screening of chemical activators and inhibitors for mammalian NAD biosynthesis. Another aspect of the invention provides a method of identifying a compound that effects in vivo activity of NAD metabolic enzymes. Further aspects of the invention include nucleic acid sequences, vectors, and transformed cells that can be used in the methods described herein.

Abstract: The present invention relates to agents, and methods for identifying compounds, which agents and compounds are effective in the treatment, and more particularly, that inhibit cachexia, and its associated or related disorders and conditions. In addition, the invention relates to compositions and methods for the use thereof in treating conditions that are characterized by cachexia, and its associated or related disorders and conditions and/or cachexia, and its associated or related disorders and conditions, such as for example, cancer cachexia and cachexia associated with AIDS, autoimmune disorders, drug addiction, alcoholism, chronic inflammatory disorders, cirrhosis of the liver, anorexia and neurodegenerative disease. In particular, the diagnostic marker and drug target of the invention is the ATGL Lipase, which can be inhibited by e.g. siRNAs and compounds with any of the following structures (I).

Abstract: An aminocoumarin conjugated to a fluorescent label through a secondary amine, is operative as a fluorescent polarization probe of the DNA gyrase B or topoisomerase IV E subunit. The probe is used for detecting topoisomerase inhibitor binding by fluorescence polarization, particularly in a high-through put topoisomerase inhibitor assay.

Abstract: This disclosure is directed to methods and compositions to inhibit MASP protein activity using small molecule inhibitors. In one aspect, the disclosure is directed to methods for identifying inhibitors of MASP protein activity, including methods of screening capable of inhibiting MASP protein activity.

Abstract: The invention provides methods and compositions for detecting dicarboxylic acids using a transcription factor biosensor.

Abstract: The invention relates to the discovery and characterization of mannan binding lectin-associated serine protease-2 (MASP-2), a new serine protease that acts in the MBLectin complement fixation pathway.

Abstract: This invention provides an isolated mutant atpE protein and departing from said mutant atpE protein the identification of an ATPase binding domain. This invention also provides related nucleic acids, vectors, host cells, pharmaceutical compositions and articles of manufacture. This invention further provides methods for determining whether a test compound interacts with an atpE protein, i.e. with the ATPase binding domain of the present invention, as well as pharmaceuticals compositions comprising said test compound, in particular as antimicrobials, more particular as antimycobacterial agent, even more particular for treating tuberculosis in a subject.

Abstract: The present invention relates to a carbapenemase and methods using said carbapenemase such as screening methods, predictive methods and therapeutic uses.

Abstract: A progesterone regulator capable of modulating the non-genomic action of progesterone and methods of using the progesterone regulator are described. The progesterone regulator is useful for attenuating progesterone's inhibition of apoptosis and for the treatment of patients having a progesterone-responsive tissue disease such as endometriosis or cancer, particularly ovarian cancer, as well as for diagnosis, prognosis, and/or staging of ovarian cancers.

Abstract: The present invention provides a composition comprising an IP3 receptor-binding protein (IRBIT), a nucleic acid that controls the expression and translation of IRBIT, or an antibody against IRBIT for controlling at least one intracellular biological function selected from the group consisting of (1) protein synthesis, (2) phosphatidylinositol metabolism, and (3) intracellular pH.

Abstract: The present invention relates to aminopeptidase N (APN) inhibitor conjugates of formula I wherein W is a —CO— or an —SO2— group and at least one of R1 or R2 represents (OCH2—CH2)n-X, where n is an integer of 1 to 100 and X represents H or a detectable label or a therapeutic, and the other represents an alkoxy group or OH, and wherein R3, R3? and R3? is independently selected from an alkoxy group or (OCH2—CH2)n-X, where n is an integer of 1 to 100 and X represents H or a detectable label or a therapeutic, and R4 is selected from the group comprising: wherein R is an alkyl group. Furthermore, the present invention relates to a diagnostic and/or pharmaceutical composition comprising the conjugate of the invention.

Abstract: The invention relates to a method of identifying a modulator of an EHD family polypeptide, said method comprising (i) providing a first and second sample of an EHD polypeptide; (ii) contacting said first sample with a candidate modulator; (iii) contacting said first and second samples with ATP; and (iv) monitoring ATP hydrolysis in said first and second samples, wherein a difference between the ATP hydrolysis in said first and second samples identifies said candidate modulator as a modulator of an EHD family polypeptide. The invention also relates to methods of modelling molecules and to various EHD mutant polypeptides.

Abstract: In certain aspects, the present invention provides BMP10 propeptides for use in treating a variety of disorders including heart disorders and other disorders associated with unwanted activity of the mature BMP10 polypeptide. The present invention also provides methods of screening compounds that modulate activity of BMP10.

Abstract: The present invention relates to a method of screening for a compound that regulate SUMOylation of the nuclear receptor proteins comprising contacting the compound of interest to the nuclear receptor protein, and detecting SUMOylation of the nuclear receptor protein, thereby screening for a compound that regulates SUMOylation.

Abstract: A method of identifying an antifungal agent which targets a PPTB protein of a fungus comprising determining whether a candidate compound binds to or inhibits a PPTB protein, wherein binding or inhibition indicates that the candidate sub-stance is an antifungal agent.

Abstract: Methods for screening molecules that modulate the activity of Retinol Binding Protein 4 (RBP4) and their use in treatment of insulin resistance are described. Also described are methods of diagnosing insulin resistance and related conditions by detecting modulation of RBP4 activity.

Abstract: Provided are purified compounds comprising SEQ ID NO:1, where the tyrosine at residue (10) is phosphorylated. Also provided are purified compounds comprising SEQ ID NO:1, where the amino acid sequence of the compound is less than 400 amino acids. Additionally provided are methods of determining whether an agent is a candidate inhibitor of an Abl kinase. Further provided are methods of inhibiting an Abl kinase. Also provided are methods of treating a patient having a condition characterized by a mutant Abl kinase. Additionally provided are methods of treating a patient at risk for a condition characterized by a mutant Abl kinase. Methods of labeling an Abl kinase are also provided. Additionally, methods of isolating an Abl kinase from a tissue are provided.

Abstract: Novel glutaminyl-peptide cyclotransferase-like proteins (QPCTLs), which are isoenzymes of glutaminyl cyclase (QC, EC 2.3.2.5), and to isolated nucleic acids coding for these isoenzymes, all of which are useful for the discovery of new therapeutic agents, for measuring cyclase activity, and for determining the inhibitory activity of compounds against these glutaminyl cyclase isoenzymes.

Abstract: Chemically reactive dyes that are intramolecularly crosslinked with a water-soluble bridge, their bioconjugates and their uses are described. Reactive fluorescent dyes that have a water-soluble bridge are superior to those of conjugates of spectrally non-crosslinked dyes or the dyes that are crosslinked with a hydrophobic bridge. The invention includes reactive fluorescent dyes, their biological conjugates and uses.

Abstract: The invention provides compositions for inhibiting a redox-sensitive GTPase protein, including a Rho or Rab family GTPase, comprising an effective amount of a redox-sensitive purine compound and an effective amount of a redox agent. The invention further provides methods of inhibiting a redox-sensitive GTPase protein, including a Rho or Rab family GTPase, by administering compositions of the invention. Methods of screening for compounds that inhibit a redox-sensitive GTPase protein, including compounds that target and inhibit Rho or Rab family GTPases, are further provided.

Abstract: A previously unrecognized fundamental property of ?1PI is to regulate the phenotypic composition of circulating and tissue-associated cells derived from hematopoietic stem cells. The present invention comprises screening for various unmodified and modified ?1PI's which are useful in the treatment of abnormalities in the number of cells of myeloid or lymphoid lineage that are associated with HW-1 infection, microbial infection, leukemia, solid tumor cancers, atherosclerosis, autoimmunity, stem cell transplantation, organ transplantation, and other diseases affected by cells of the immune system. The interaction of ?1PI with its receptors, HLECS and LRP, influences the level of cells of different lineages. Genetic and proteolytic modification of ?1PI is used to target these receptors to increase or decrease specific cell populations, as needed, in the various disease states.

Abstract: The present invention relates to nucleic acid molecules encoding Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to antibodies or portions thereof that specifically bind Neutrokine-alpha and/or Neutrokine-alphaSV and diagnostic and therapeutic methods using these antibodies. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders using the compositions of the invention.

Abstract: Described herein are irreversible kinase inhibitor compounds, methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate irreversible inhibitor of a protein, including a kinase.

Abstract: The present invention relates to the discovery, identification and characterization of nucleotide sequences that encode novel substrate-targeting subunits of ubiquitin ligases. The invention encompasses nucleotides encoding novel substrate-targeting subunits of ubiquitin ligases, and transgenic mice, knock-out mice, host-cell expression systems and proteins encoded by the nucleotides of the novel substrate-targeting subunits. The present invention relates to screening assays that use novel and known substrate-targeting subunits of ubiquitin ligases to identify potential therapeutic agents such as small molecules, compounds or derivatives and analogues of the novel and known ubiquitin ligases which modulate activity of the novel and known ubiquitin ligases for the treatment of proliferative and differentiative disorders, such as cancer, major opportunistic infections, immune disorders, certain cardiovascular diseases, and inflammatory disorders.

Abstract: The present invention relates to USP47 (ubiquitin specific protease 47) inhibitors and methods for inducing apoptosis or cell death in a target cell. In certain embodiments, the invention relates to methods and kits to screen for related agents that induce apoptosis. Additionally, the invention relates to assays for screening compounds capable of acting as USP47 inhibitors.

Abstract: A conjugate which comprises a cyclosporin moiety of formula (I) linked to one or more mitochondrial targeting groups, or a pharmaceutically acceptable salt thereof: wherein: A represents or, B represents methyl or ethyl, one Of R1 and R1 represents hydrogen and the other represents methyl, R2 represents ethyl or isopropyl, R3 represents hydrogen or methyl, and R4 represents —CH2CH(CH3)CH3, —CH2CH(CH3)CH2CH3, —CH(CH3)CH3 or —CH(CH3)CH2CH3.

Abstract: Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic plants and animals.

Abstract: An enzyme detection device (1) for detecting the presence, in a sample, of an enzyme capable of modifying a provided substrate (10). The device (1) comprises a substrate which has a modification region (14) that is sensitive to modification by the enzyme from an unmodified state to a modified state. The device (1) further comprises a substrate recognition molecule (16) which binds the modification region (14) in either the modified or the unmodified state. The modification region 14 of the substrate is preferentially bound by the substrate recognition molecule (16) as compared with the enzyme when mixed. The device further comprises a detectable label (18) coupled to the substrate recognition molecule (17).

Abstract: Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

Abstract: An objective of the present invention is to provide methods of testing for acute ischemic diseases using active hepcidin as an indicator, methods for determining the timing to administer an agent for treating the disease, and kits for these methods. To accomplish the objective, the present inventors analyzed the serum proteome patterns characteristic of acute myocardial infarction patients using SELDI-TOF-MS. As a result, it was found that hepcidin-20 has a very high correlation with acute myocardial infarction. Furthermore, the present inventors discovered that at the time of disease onset, the blood concentration of hepcidin-20 rises sharply in particular, and shows high levels within six hours, especially four hours of onset. The present invention enables early diagnosis of acute ischemic diseases.

Abstract: A prenatal method of analyzing a fetus is disclosed. The method comprising: (a) isolating placental derived microparticles; and (b) analyzing at least one component of the contents of the placental derived microparticles, wherein the at least one component is indicative of a characteristic of the fetus.

Abstract: Antibodies which bind an antigen of the bone marrow neovasculature in leukaemia patients, for use in treatment and diagnosis of leukaemia, in particular the treatment and diagnosis of acute myeloid leukaemia (AML).

Abstract: Compositions and methods for reducing hepatitis C virus (HCV) replication are provided. Also provided are compositions and methods of treating an HCV infection; methods of reducing the incidence of complications associated with HCV and cirrhosis of the liver; and methods of reducing viral load, or reducing the time to viral clearance, or reducing morbidity or mortality in the clinical outcomes, in patients suffering from HCV infection.

Abstract: The present invention provides a synthetic regulator of glutamate receptor function, which regulator is a light-sensitive (photoreactive) regulator. The present invention further provides a light-regulated glutamate receptor that includes a subject synthetic regulator non-covalently associated with the glutamate receptor. Also provided are cells and membranes comprising a subject light-regulated glutamate receptor. The present invention further provides methods of modulating glutamate receptor function, involving use of light. The present invention further provides methods of identifying agents that modulate glutamate receptor function.

Abstract: The present application relates to compositions and the treatment of skin disorders, dry skin, protection of skin in inflammatory events and neurological disorders. The present application more particularly discloses the identification of new genes and metabolic pathways involved in skin disorders, which provide novel targets and approaches for treating said disorders and for screening biologically active compounds. The present invention also provides various products and constructs, such as probes, primers, vectors, recombinant cells, which can be used to implement the above methods. The invention may be used to detect or treat various skin disorders, particularly dry and inflammatory skin disorders and neurological disorders, in various subjects, including mammalian subjects, particularly human beings.

Abstract: The invention features methods for the identification of leucine-rich kinase 2 (LRRK2) inhibitors using indol ligand 91. Generally, these methods include identifying compounds that compete with indol ligand 91 for binding to LRRK2.

Abstract: The present invention provides compositions and methods for detecting the activation states of components of signal transduction pathways in tumor cells. Information on the activation states of components of signal transduction pathways derived from use of the invention can be used for cancer diagnosis, prognosis, and in the design of cancer treatments.

Abstract: The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

Abstract: Materials and Methods related to diagnosing a clinical condition in a subject, or determining the subject's predisposition to develop the clinical condition, using a multi-parameter system to measure a plurality of parameters and an algorithm to determine a disease score.

Abstract: Methods and reagents are disclosed for conducting assays. Embodiments of the present methods and reagents are concerned with a solid support such as, for example, a particle. The support includes a chemiluminescent composition that includes a metal chelate. The present inventors observed that, when such support such as, e.g., particles, were employed in assays for the determination of an analyte, stability of signal output by the chemiluminescent composition associated with the particle was unacceptably reduced as compared to particles including other chemiluminescent compositions. In accordance with embodiments of the present invention, the stability of signal output from such particles is enhanced by including in a medium that contains the particles a sufficient amount of one or more stabilizing agents, which may be a chelating agent and/or a metal chelate such as, for example, the metal chelate that is associated with the particle.

Abstract: The present invention relates to immobilization compounds (I), immobilization products and preparations thereof as well as methods and uses for the identification of kinase interacting compounds or for the purification or identification of kinase proteins.

Abstract: The atypical antipsychotic drugs (AAPDs) have markedly enhanced the treatment of schizophrenias but their use has been hindered by the major weight gain elicited by some AAPDs. We found that orexigenic AAPDs potently and selectively activate hypothalamic AMP kinase (AMPK), an action abolished in mice with deletion of histamine H1 receptors. These findings afford a means of developing better therapeutic agents and provide insight into the hypothalamic regulation of food intake.

Abstract: THE INVENTION RELATES TO compositions, compounds, proteins and methods of treatment therewith. Aspects of embodiments also relate to a method of treating a patient by delivering to the tissues of said patient or administering to said patient a therapeutically effective amount of one or more compounds. Aspects of embodiments also relate to a method of detecting the presence of bone disease by machine-assaying detectable serotonin. Aspects of embodiments also relate to methods of treating disease in subjects.

Abstract: The invention provides for a novel cholesterol loaded insect cell membrane preparation having an increased cholesterol level as compared to physiological cholesterol levels of insect cell membranes or to control insect cell membrane preparations without cholesterol loading, wherein said cholesterol loaded membrane preparation comprises an ABC transporter protein having an increased substrate transport activity due to increased cholesterol level of the membrane. The invention also relates to reagent kits comprising the preparations of the invention. The invention also relates to methods for manufacturing said preparations and methods for measuring any type of activity of the ABC transporters present in the cholesterol loaded membranes as well as studying or testing compounds and interaction of compounds and ABC transporters, in this assay systems. The invention also provides for a test system useful for testing whether ABC transporter proteins can be activated by cholesterol in an insect cell membrane.

Abstract: The invention relates to a method for diagnosing, staging and/or monitoring a hemoglobin-related disorder such as ?-thalassemia or a treatment against said hemoglobin-related disorder in a subject in need thereof based on the detection and/or quantification the presence of free ?-Hb pool in a biological sample obtained from said subject.

Abstract: The present invention relate to methods of identifying a genotype-selective agent. In certain embodiments, the invention relates to agents that are selectively toxic to engineered human tumorigenic cells.

Abstract: Disclosed herein are methods of diagnosing, preventing and treating Alzheimer's disease based on the use of an inhibitor for the binding of amyloid-? (A?) to Fc?RIIb, and a method of screening the inhibitor. The inhibitor is selected from the group consisting of an Fc?RIIb protein or a variant thereof, an Fc?RIIb extracellular domain, an anti-Fc?RIIb antibody, an Fc?RIIb-specific peptide and an Fc?RIIb-specific siRNA. The inhibitor reduces the toxic signaling and intracellular translocation of A? and the neurotoxicity, neuronal cell death and memory impairment mediated by A? by inhibiting the binding between A? and Fc?RIIb. Thus, the inhibitor is useful in the diagnosis, prevention and treatment of Alzheimer's disease.

Abstract: The present invention concerns a method for the simultaneous detection of different bacteria, comprising the following steps: coupling one or more species of bacteriophage tail proteins onto a support, incubating the support coupled with the bacteriophage tail proteins with a sample, optionally removing the sample and the bacteria of the sample not bound to the bacteriophage tail proteins, contacting the bacteria bound to the bacteriophage tail proteins with the bacteriophages and/or bacteriophage proteins specifically binding the bacteria to be detected, removing the bacteriophages and/or bacteriophage proteins not bound to the bacteria, and performing the detection reaction by means of an enzyme coupled to the specifically binding bacteriophages and/or bacteriophage proteins or by means of an immuno assay.