Abstract: The present invention provides methods and compositions for modulating the activity of phosphodiesterase 1B (PDE1B) in intracellular signaling pathways, including but not limited to, dopamine D1 intracellular signaling pathways. The invention also provides methods and compositions for modulating the activities of intracellular signaling molecules, including, but not limited to, DARPP-32 and GluR1 AMPA receptor, via modulation of PDE1B. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate PDE1B activity. The invention also provides methods of treating or ameliorating the symptoms of a disorder, including but not limited to a PDE1B-related disorder or a dopamine D1 receptor intracellular signaling pathway disorder, by administering a modulator of PDE1B, preferably, but not limited to, an inhibitor of PDE1B or an agent that decreases the production of PDE1B.

Abstract: The present invention provides a method for lowering intraocular pressure and providing neuroprotection to a patient in need thereof by administering a therapeutically effective amount of at least one non-nucleotide or non-protein agent that inhibits expression and/or signaling of connective tissue growth factor (CTGF).

Abstract: Regulation of striatal indirect pathway endocannabinoid-mediated long-term depression (eCB-LTD) is used to improve motor deficits of striatal-based brain disorders. In such treatment, a dopamine D2 receptor agonist is administered in conjunction with an inhibitor of endocannabinoid degradation. In some embodiments, the inhibitor of endocannabinoid degradation is a fatty acid amine hydrolase inhibitor, or a monoacylglycerol lipase antagonist. The combination provides for a synergistic effect, with improved therapeutic effects. Also provided are kits and systems for practicing the subject methods, as well as methods of use of agents identified in the screening method of the invention.

Abstract: The present invention provides methods for identifying agents that modulate a level or an activity of a mitochondrial NAD-dependent deacetylase polypeptide, as well as agents identified by the methods. The invention further provides methods of modulating mitochondrial NAD-dependent deacetylase activity in a cell. The invention further provides methods of modulating mitochondrial function by modulating the activity of mitochondrial NAD-dependent deacetylase.

Abstract: A method and solution for perioperatively inhibiting a variety of pain, inflammation, spasm and restenosis processes resulting from cardiovascular or general vascular therapeutic and diagnostic procedures. The solution preferably includes multiple pain and inflammation inhibitory agents and spasm inhibitory agents at dilute concentration in a physiologic carrier, such as saline or lactated Ringer's solution. Specific preferred embodiments of the solution of the present invention for use in cardiovascular and general vascular procedures also include anti-restenosis agents. The solution is introduced luminally to continuously irrigate an arterial site during an operative/interventional or diagnostic procedure for preemptive inhibition of pain and inflammation, vascular and non-vascular smooth muscle spasm, and restenosis while avoiding undesirable side effects associated with oral, intramuscular, subcutaneous or intravenous application of larger doses of the agents.

Abstract: The present invention provides a method for assessing bowel function in a patient, comprising providing the patient with a numeric analog scale for at least one parameter which is a measure of bowel function; causing the patient to indicate on the numeric analog scale the amount and/or intensity of the parameter being experienced; and observing the amount and/or intensity of the at least one parameter indicated on the numeric analog scale in order to assess bowel function.

Abstract: Detection of expression of the provided phosphatases in cancers is useful as a diagnostic, for determining the effectiveness of drugs, and for determining patient prognosis. The encoded polypeptides further provide a target for screening pharmaceutical agents effective in inhibiting the growth or metastasis of tumor cells. The present invention further provides methods and compositions relating to agents that specifically bind to MKPX, PTP4A1, PTPN7, FEM-2, DKFZP566K0524 or FLJ20313 for treatment and visualization of tumors in patients.

Abstract: The invention provides modulators of Dvl PDZ-ligand interaction, and methods of identifying and using these modulators.

Abstract: The present invention relates to crystals comprising human PCNA, and methods and assays for designing and identifying small molecule PCNA inhibitors using said crystals.

Abstract: The present invention describes methods to identify compounds that prevents or treat amyloid accumulation in the brain, as mediated by microglia or cells of macrophage lineage. The present invention further describes compositions containing such compounds, methods of preparing such compositions and methods of using such compositions. The compositions are useful for treating or preventing diseases caused by or associated with cell-mediated amyloid formation, and are particularly useful in treating or preventing neurodegenerative diseases, such as Alzheimer's Disease and bovine spongiform encephalopathy.

Abstract: An isolated or purified nucleic acid molecule consisting essentially of a nucleotide sequence encoding the metastasis suppressor gene located at p21-p12 on chromosome 8 of a human (Tey 1), a variant Tey 1, or a fragment of either of the foregoing comprising at least 455 contiguous nucleotides; an isolated or purified nucleic acid molecule consisting essentially of a nucleotide sequence that is complementary to a nucleotide sequence encoding Tey 1, a variant Tey 1, or a fragment of either of the foregoing comprising at least 455 contiguous nucleotides; a vector comprising any of the foregoing, wherein, when the isolated or purifies nucleic acid molecule consists essentially of a nucleotide sequence encoding Tey 1 or a variant thereof, the isolated or purified nucleic acid molecule is optionally part of an encoded fusion protein; a cell comprising and expressing any of the foregoing isolated or purified nucleic acid molecules, optionally in the form of a vector; an isolated or purified polypeptide molecule cons

Abstract: An in vivo screening assay for identifying an agent that interferes with T cell activation and/or -differentiation and/or modulation of other inflammatory effector cells.

Abstract: The invention provides methods for detecting and monitoring diseases associated with genetic abnormalities in a subject.

Abstract: The invention provides a method of identifying a niacin receptor modulator with reduced flushing effect compared to niacin or a niacin analog, comprising determining the MAP kinase activity of said modulator, wherein a decrease in MAP kinase activity induced by said modulator compared to MAP kinase activity induced by niacin or a niacin analog indicates that said modulator has reduced flushing effect when compared to niacin or a niacin analog.

Abstract: The present invention includes compositions and methods for treating arthritic joints found in patients with autoinflammation, e.g., systemic onset juvenile idiopathic arthritis, by administering at the site of inflammation a therapeutically effective amount of at least one agent that reduces or blocks the bioavailability of interleukin-1?.

Abstract: The therapeutic use of temporary p53 inhibitors in the treatment of p53-mediated diseases, conditions, and injuries is disclosed.

Abstract: New devices and methods for diagnosis and compositions and methods for treatment of cancers use combinations of antimicrobial agents and agents that can reverse dormancy and hibernation pathways. We unexpectedly found that surprisingly low doses of anti-hibernation compounds can substantially inhibit cancer cell growth in vitro and can successfully treat cancers, including metastatic cancer. We also unexpectedly found that antimicrobial agents and anti-HDS compounds together can increase the degree of inhibition of cancer cell growth in a synergistic fashion. We conclude that combination therapy with antimicrobial agents and anti-HDS compounds can be effective in treating human patients with cancer.

Abstract: The present invention relates to prophylactic antimigraine agents comprising as an active ingredient a dual antagonist for the 5-HT2B and 5-HT7 receptors, the antagonist having a binding affinity selective for the 5-HT2B and 5-HT7 receptors. Since these prophylactic antimigraine agents show an excellent pharmacological effect in comparison with the cases in which a 5-HT2B receptor antagonist having a selective binding affinity to the 5-HT2B receptor or a 5-HT7 receptor antagonist having a selective binding affinity to the 5-HT7 receptor is used alone, they are useful as drugs which are excellent in prophylaxis of migraine and in which the side effects found in the existing prophylactic antimigraine agents are reduced.

Abstract: It is intended to provide an organ function maintaining or ameliorating solution, which is effective for suppressing the depression of an organ provided for transplantation and an organ preservation method using the organ function maintaining or ameliorating solution. The present invention relates to an organ function maintaining or ameliorating solution for maintaining or ameliorating the functions of an organ provided for organ transplantation, comprising a pharmacologically active substance comprising glycyrrhizic acid, glycyrrhetinic acid or a pharmacologically acceptable salt or derivative thereof in an organ preservation solution. The present invention also relates to a method of preserving an organ for organ transplantation comprising perfusing the organ function maintaining or ameliorating solution to the organ isolated from the donor to cause ischemia and immersing the organ in the organ function maintaining or ameliorating solution during the time until the organ is transplanted into a recipient.

Abstract: The invention relates in embodiments to methods for identifying compounds that inhibit phosphorylation of GD-1, to compositions comprising such inhibitors, including pharmaceutical compositions, and to the use of such inhibitors and compositions to treat diseases, such as inflammatory diseases.

Abstract: The present invention relates to methods for the identification of compounds that increase or decrease the inhibitory effect of TFPI on tissue factor activity and/or Factor Xa activity and/or thrombin formation. The invention also relates to methods for the identification of compounds that increase or decrease the co-factor activity of Protein S in TFPI-mediated inhibition of tissue factor and/or Factor Xa activity. This invention also relates to a pharmaceutical composition comprising the compounds identifiable by such methods. The invention also relates to methods for the regulation of tissue factor activity by influencing the interaction between Protein S and Tissue Factor Pathway Inhibitor.

Abstract: The present invention provides methods for diagnosing a neurological disease and/or for determining the predisposition of a subject to a neurological disease and/or for determining a subject at risk of developing a neurological disease, the method comprising detecting a marker in a glycogen synthase kinase 3? gene or expression product thereof and a microtubule-associated protein tau (MAPT) gene or expression product thereof. The present invention also provides pharmacogenetic methods, e.g., for identifying a subject that will respond to treatment with a therapeutic compound.

Abstract: The present invention provides screening methods for identifying agents that modulate the activity of mitochondrial aldehyde dehydrogenase-2 (AldDH2), as well as agents identified by the screening methods. The present invention further provides methods of reducing ischemic tissue damage or free-radical induced damage in an organ, the methods generally involving contacting the organ with an agent that increases AldDH2 levels and/or activity. The present invention further provides methods of treating solid tumors, the methods generally involving administering an agent that decreases AldDH2 levels and/or activity.

Abstract: Disclosed herein is a pharmaceutical composition comprising a relaxant and an alpha-2B receptor agonist. The composition is effective for treating gastrointestinal motility disorders, and methods of treating such disorders using the composition and compounds comprising it are also disclosed.

Abstract: The present invention relates to a method for providing an animal population having an essentially identical metabolome comprising compiling an animal population being of essentially the same age, keeping said animal population for a time period sufficient for acclimatization under the following housing conditions: (i) constant temperature, (ii) constant humidity, (iii) physical separation of the animals of the animal population, (iv) feeding ad libitum, wherein the food to be fed is essentially free of chemical or microbial contaminance, (v) drinking libitum, wherein the drinking liquid is essentially free of chemical or microbial contaminance, (vi) constant illumination period, and providing the animal population after said time period. Further, the present invention relates to methods for the identification of a compound which effects the metabolome of an animal, or methods for the identification of a marker for such compounds.

Abstract: Particular embodiments disclosed herein relate to electrokinetically altered gas-enriched fluids, methods of making the same, systems for making the same and/or methods of treatment utilizing the gas-enriched fluids for eye related conditions and/or diseases. In certain embodiments, the electrokinetically altered gas-enriched fluid is oxygen-enriched water. Certain embodiments relate to cosmetic and/or therapeutic fluids and/or methods of treatment utilizing the fluids to treat a cosmetic and/or therapeutic symptom related to eye conditions and/or diseases.

Abstract: A skin care delivery device is disclosed. The skin care delivery device includes a substrate containing a skin care composition. The skin care composition can comprise, for instance, any suitable lotion or other similar material. In accordance with the present disclosure, a backing is releasably engaged to one surface of the substrate. The backing facilitates folding and unfolding of the delivery device. Once applied to a user's skin, the backing can be peeled away and discarded.

Abstract: The present invention relates to a diagnostic agent for an ischemic heart disease risk group comprising an anti-brain-derived neurotrophic factor antibody as an effective ingredient, to an assay method for an ischemic heart disease risk group performed by measuring a brain-derived neurotrophic factor concentration in blood, and to a suppressive/preventive drug for ischemic heart disease, particularly for post-infarction myocardial remodeling, comprising a brain-derived neurotrophic factor.

Abstract: Provided are methods of treatment for skin disorders. In particular, treatment, the skin disorders are generally inflammatory skin disorders, including improper wound healing. Provided are methods of using of a cytokine molecule.

Abstract: Histamine H3 inverse agonists or histamine H3 antagonists are useful, alone or in combination with an anti-stroke agent, for treating stroke.

Abstract: Particular embodiments disclosed herein relate to gas-enriched fluids, methods of making the same, systems for making the same and/or methods of treatment utilizing the gas-enriched fluids for wound care related conditions and/or diseases. In certain embodiments, the gas-enriched fluid is oxygen-enriched water. Certain embodiments relate to cosmetic and/or therapeutic fluids and/or methods of treatment utilizing the fluids in order to treat a cosmetic and/or therapeutic symptom of wound care and/or increase proper wound healing.

Abstract: The invention provides methods and models for understanding how HDAC inhibitors interact with antifungal azole compounds to potentiate the activity of such compounds, using fungal strains which have selective knockouts of fungal HDAC genes. The invention further provides methods for testing antifungal agents for potential synergy with fungal HDAC inhibitors, and thus provides antifungal compound which are identified according to the methods of the invention, and methods for treatment of fungal infections using such compounds.

Abstract: A new method of evaluating the ability of drug molecules to penetrate the cornea is described. The permeation rate of the drug molecules in MDCK cells is utilized to predict the ability of the molecules to penetrate the cornea. The method is useful for in vitro screening of potential new ophthalmic drugs, as well as in the design of new drug molecules for topical ocular administration.

Abstract: An oral drug delivery system comprising a coated tablet having one or more surfaces. The coated tablet further comprises a core and a coating surrounding the core. The core comprises an active ingredient composition comprising at least one active ingredient and a pharmaceutically acceptable excipient and a composition selected from a swellable composition and a reactive composition located in an immediate vicinity of one or more preselected surfaces. The coating comprising water insoluble polymer(s) and leachable component(s) is operable to be reliably removed fully from the one or more of the preselected surfaces of the tablet upon contact with an aqueous environment, but not removed from at least one of the surfaces.

Abstract: Compositions having a curable unsaturated compound, an adhesion promoter and curing agent which have a peak exotherm of less than 50° C. are disclosed. The compositions when cured are flexible bioadhesives which are also disclosed. Non-curable diluents can be included in the compositions. Flexible bioadhesives formed on biological structures and having low peak exotherms upon curing of curable compositions to form the flexible bioadhesives are disclosed. Compositions having a curable unsaturated compound and a curing agent and a peak exotherm of less than 50° C. are included in the invention.

Abstract: The invention relates to the use of methionine synthase inhibitors for the treatment of fungal diseases of crops. The invention further relates to methods for treatment of crops against fungal diseases comprising the application of a methionine synthase inhibitor also methods for the identification of novel fungicidal compounds comprising a step for identification of methionine synthase inhibitors.

Abstract: The present invention relates to methods for determining the potential of a subject to respond to a particular therapeutic agent, by determining the presence of one or more nucleotide or amino acid variants in the ?-tubulin gene or protein. Also provided are methods for treating subjects whose potential to respond to a therapeutic agent has been evaluated. For use in the methods of the invention, there are provided variants of the ?-tubulin gene, variants of the ?-tubulin protein, nucleic acid molecules and agents which bind to the variant ?-tubulin nucleic acid molecules and variant ?-tubulin protein, respectively, and kits comprising the same.

Abstract: The present invention is directed to a method of screening for a carnitine transporter agonist or for a carnitine transporter antagonist, to a kit for carrying out the method of screening for a carnitine transporter agonist or for a carnitine transporter antagonist, to a method for the manufacture of a medicament for the treatment of a carnitine transporter deficiency, to methods of diagnosis of a carnitine transporter deficiency, to the use of a protein for the manufacture of an antibody reacting with a carnitine transporter, to an oligonucleotide and to methods of treatment of a carnitine transporter deficiency.

Abstract: The present invention relates to the use of an inhibitor of CDK2 and/or CDK7 and/or CDK9, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating a disease associated with antinuclear antibodies, wherein the inhibitor of CDK2 and/or CDK7 and/or CDK9 or pharmaceutically acceptable salt thereof is administered in an amount sufficient to down-regulate the levels of antinuclear antibodies. A further aspect of the invention relates to a combination comprising an inhibitor of CDK2 and/or CDK7 and/or CDK9, or a pharmaceutically acceptable salt thereof, and methylprednisolone, and its use in the treatment of diseases associated with antinuclear antibodies, such as SLE.

Abstract: The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In certain embodiments, the GPCR is human. In certain embodiments, the GPCR is expressed endogenously by neuronal cells or muscle cells. In certain embodiments, the GPCR is neuroprotective or myoprotective. In certain embodiments, the GPCR is a Humanin receptor. The present invention also relates to methods of using a modulator of said GPCR. A preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of neurodegenerative diseases in general, including Alzheimer's disease, Parkinson's disease, prion-associated disease, stroke and motor-neuron disease in particular, peripheral neuropathy, cerebral amyloid beta-protein angiopathy, and ischemic heart disease, including myocardial infarction and congestive heart failure.

Abstract: The present invention features methods for treating and/or preventing neurodegenerative and/or neurotoxic diseases, conditions, and injuries, by inhibiting the activity of protease-activated receptor-1 (PAR1) on neurons and glial cells using PAR1 antagonists.

Abstract: The present invention is directed to FAAH crystals in complex with the inhibitor methoxyarachidonyl fluorophosphonate (MAFP) and to the use of these crystals to determine the three-dimensional structure of FAAH. This invention id further directed to the use of this structure for the modeling or determination of the structures of related proteins. This invention is further directed to the use of this structure in the pursuit of drug design to identify, characterize, or optimize agents which bind to the active site, substrate channels, product channels, or regulatory sites of FAAH, and to the evaluation of these agents to identify agents which may stimulate, inhibit, relocalize, stabilize, or destabilize FAAH and/or its activity. This invention is further directed to the use of this structure in the development of engineered FAAH variants which display altered solubility, catalytic profiles, or substrate specificity.

Abstract: The present invention shows that pharmacological up regulation of SRB-1, ABC-A1 and LCAT genes collectively can be used to promote reverse cholesterol transport and increase circulating HDL cholesterol as treatment for atherosclerosis and related cardiovascular disorders.

Abstract: The Wnt signaling pathways are involved in embryo development as well as in tumorigenesis. Dishevelled (Dvl) tranduces Wnt signals from the receptor Frizzled (Fz) to downstream components in canonical and non-canonical Wnt signaling pathways, and the Dvl PDZ domain plays an essential role in both pathways, and the Dvl PDZ domain binds directly to Fz receptors. In the present invention using NMR-assisted virtual ligand screening, several compounds were identified and were found to bind to the Dvl PDZ domain. Molecular dynamics simulation was used to analyze the binding between the PDZ domain and these compounds in detail. These compounds provide a basis for rational design of high-affinity inhibitors of the PDZ domain, which can block Wnt signaling by interrupting the Fz-Dvl interaction.

Abstract: The present invention provides compositions and methods for inhibiting protozoan growth comprising a synergistic combination of lipid synthesis inhibitors. In addition, the invention provides compositions and methods that are useful for the treatment of protozoan infections and the identification of potential new drugs for the treatment of protozoan infections.

Abstract: The present invention relates to methods and compositions for modulating ADPR-mediated migratory activity of cells through regulation of the TRPM2 cation channel. Such methods and compositions may be used for the treatment of disorders including, but not limited to, inflammation, ischemia, atherosclerosis, asthma, autoimmune disease, diabetes, arthritis, allergies, and transplant rejection. Such cells include, for example, neutrophils, lymphocytes, eosinophils, macrophages, monocytes and dendritic cells. The invention further relates to specific inhibition of TRPM2 by blocking the activity of ADPR. The invention also relates to drug screening assays designed to identify compounds that regulate TRPM2 and thereby also function to modulate ADPR-mediated cell migration. The invention is based on the discovery that, 8Br-ADPR, which specifically inhibits activation of TRPM2, acts to inhibit ADPR-mediated cell migration.

Abstract: Described herein are methods for treating a subject suffering from a T-cell lymphoma by administering to the subject a pharmaceutical composition containing a therapeutically effective amount of a selective inhibitor of histone deacetylase 8. Also described herein are methods for treating a subject suffering from a T-cell lymphoma by administering to the subject a population of autologous T-cells that have been exposed to a selective HDAC8 inhibitor composition ex vivo.

Abstract: It is intended to identify rheumatoid arthritis susceptibility genes by a highly efficient, low-cost mapping method using microsatellites. In the present invention, novel rheumatoid arthritis susceptibility genes, that is, TNXB, NOTCH4, RAB6A, MPRL48, UCP2, and UCP3 genes, in the human genomic DNA sequence were identified by conducting case-control association analysis on rheumatoid arthritis by use of microsatellite polymorphic markers assigned at approximately 100-kb intervals to narrow down candidate regions and then conducting association analysis and linkage analysis with SNP as a marker.

Abstract: The present invention comprises a plurality of injectable hollow particulate fillers suspended in a biocompatible fluid carrier to significantly improve the clumping resistance and injectability of the composition. The hollow particulate fillers have a lower effective density and are able to suspend in the carrier without precipitation. The loss of skin volume as a result of aging, diseases, weight loss, and injury can lead to uneven skin surface (e.g. wrinkle, etc.). The uneven skin can be repaired by injecting appropriate amount of hollow fillers underneath the skin. Some cases of urinary incontinence occur when the resistance to urine flow has decreased excessively. Continence is restored by injecting the present invention to the urethra tissue to increase resistance to urine outflow. Similarly, the present invention allows for the control of gastric fluid reflux by submucosal injections of the fillers to the esophageal-gastric and gastric-pyloric junction.

Abstract: The invention relates to the Slug gene, the replication, transcription or expression products thereof and products related with the regulation of said Slug gene or with the regulation, elimination or degradation of the expression or translation products of same, which can be used in the identification, prevention or treatment of the spread or development of metastasis in cancer patients, such as a patient suffering from a cancer with cancer cells that express the Slug gene.