Abstract: Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

Abstract: Described herein are compositions and uses thereof related to Ca2+ release-activated Ca2+ (CRAC) channel activity. Also described herein CRAC channel modulators for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

Abstract: An automated detection system includes a robotic fluid handling system for performing a plurality of assays; a detection system for imaging the assays as they are performed; and a computer control, data acquisition, and data analysis system for controlling the operation of the fluid-handling and detection system and for collecting and analyzing imaging data. The automated detection system comprises a pipettor for simultaneously distributing a predetermined amount of a liquid and a signal-generating element to each of the plurality of wells; an excitation source for simultaneously exposing the wells to excitation radiation; a detector for simultaneously detecting signal emitted from each of the wells over a period of time comprising a single imager for optically imaging the plurality of wells simultaneously; and computerized controller for simultaneously coordinating the pipettor, the excitation source, and the detector.

Abstract: Methods are provided for identifying agents that modulate intracellular calcium. Also provided are methods of modulating calcium within cells and methods of identifying proteins involved in modulating intracellular calcium.

Abstract: Isolated nucleic acid molecules containing polymorphisms in genes involved in neurodegenerative diseases are provided. Probes, primers, kits and methods for detection of polymorphisms in genes involved in neurodegenerative disease are provided. Methods based on detecting such polymorphisms for prognosticating, determining the occurrence, profiling drug response and drug discovery are also provided. Methods of screening for agents that modulate expression and/or activity of genes involved in neurodegenerative diseases, and of screening for agents that modulate a biological event characteristic of a neurodegenerative disease are further provided.

Abstract: An automated detection system includes a robotic fluid handling system for performing a plurality of assays; a detection system for imaging the assays as they are performed; and a computer control, data acquisition, and data analysis system for controlling the operation of the fluid-handling and detection system and for collecting and analyzing imaging data. The automated detection system comprises a pipettor for simultaneously distributing a predetermined amount of a liquid and a signal-generating element to each of the plurality of wells; an excitation source for simultaneously exposing the wells to excitation radiation; a detector for simultaneously detecting signal emitted from each of the wells over a period of time comprising a single imager for optically imaging the plurality of wells simultaneously; and computerized controller for simultaneously coordinating the pipettor, the excitation source, and the detector.

Abstract: An automated detection system includes a robotic fluid handling system for performing a plurality of assays; a detection system for imaging the assays as they are performed; and a computer control, data acquisition, and data analysis system for controlling the operation of the fluid-handling and detection system and for collecting and analyzing imaging data. The automated detection system comprises a pipettor for simultaneously distributing a predetermined amount of a liquid and a signal-generating element to each of the plurality of wells; an excitation source for simultaneously exposing the wells to excitation radiation; a detector for simultaneously detecting signal emitted from each of the wells over a period of time comprising a single imager for optically imaging the plurality of wells simultaneously; and computerized controller for simultaneously coordinating the pipettor, the excitation source, and the detector.

Abstract: Compositions and methods are provided for identifying agents that alter mitochondrial membrane permeability transition. The screening methods generally detect agents that alter the interaction between the mitochondrial adenine nucleotide translocator and cyclophilin D. Such agents may be used, for example, in the treatment of a variety of conditions associated with altered mitochondrial function.

Abstract: Compositions and methods are provided for identifying agents that alter mitochondrial membrane permeability transition. The screening methods generally detect agents that alter the interaction between the mitochondrial adenine nucleotide translocator and cyclophilin D. Such agents may be used, for example, in the treatment of a variety of conditions associated with altered mitochondrial function.

Abstract: An automated detection system includes a robotic fluid handling system for performing assays on the plurality of test samples; a detection system for imaging the assays as they are performed; and a computer control, data acquisition, and data analysis system for controlling the operation of the detection system and for collecting and analyzing imaging data.

Abstract: The present invention is related to the discovery of several single nucleotide polymorphisms (SNPs) and/or mutations in the Alpha-2-Macroglobulin gene (A2M), which are risk factors for Alzheimer's Disease (AD). More specifically, aspects of the invention concern nucleic acids corresponding to the A2M gene or fragments thereof, which contain one or more of the SNPs and/or mutations described herein, peptides or proteins encoded by said nucleic acids, antibodies to said peptides or proteins and methods of making said compositions, diagnostic methods, methods of data analysis, and pharmaceutical discovery and preparation methods.

Abstract: Methods are provided for identifying agents that modulate intracellular calcium. Also provided are methods of modulating calcium within cells and treating disease by modulating intracellular calcium. Also provided are methods of screening for nucleic acids encoding candidate ion transport proteins and methods of identifying nucleic acids encoding ion transport proteins.

Abstract: Probes, primers and kits for detection of polymorphisms in genes involved in neurodegenerative disease are provided. Methods based on detecting such polymorphisms for prognosticating, determining the occurrence, profiling drug response and drug discovery are also provided.

Abstract: A compound of formula I wherein X represents an optionally halo-substituted (C2-4)alkynylene group bonded via vicinal unsaturated carbon atoms.

Abstract: Genetic markers associated with Alzheimer's disease are provided. Also provided are methods of determining the presence or absence in a subject of one or more polymorphisms associated with Alzheimer's disease and methods of determining the level of risk for Alzheimer's disease in a subject. Further provided are nucleic acid compositions and kits for use in determining the presence or absence in a subject of one or more polymorphisms associated with Alzheimer's disease and kits for determining the level of risk for Alzheimer's disease in a subject.

Abstract: The present invention is related to the discovery of several single nucleotide polymorphisms (SNPs) and/or mutations in the Alpha-2-Macroglobulin gene (A2M), which are risk factors for Alzheimer's Disease (AD). More specifically, aspects of the invention concern nucleic acids corresponding to the A2M gene or fragments thereof, which contain one or more of the SNPs and/or mutations described herein, peptides or proteins encoded by said nucleic acids, antibodies to said peptides or proteins and methods of making said compositions, diagnostic methods, methods of data analysis, and pharmaceutical discovery and preparation methods.

Abstract: Automated measurement apparatus and methods for automated drug screening procedures are provided. The apparatus is capable of initiating and measuring rapid or transient events, such as cell receptor and/or ion channel activity. In particular, the apparatus is capable of aligning with predetermined positions, one or more samples contained in a multi-well container, initiating the reaction with reagent addition and measuring a resultant attribute for a period of time. The apparatus can substantially continuously measure and record data corresponding to the measured attribute before, during and after initiation of the reaction so that a time course of the rapid or transient event may be determined. After the reaction(s) are complete in one or more wells of the multi-well container, the apparatus can align one or more different wells to be assayed with the predetermined position and repeat the cycle until a predetermined number of wells are assayed.

Abstract: The invention provides methods for screening for agents that modulate mitochondrial membrane potential. Such agents generally bind to a peripheral benzodiazepine receptor and may be detected by direct binding assays or by indirect or functional assays. Agents identified using the screens provided herein have application in the prevention and treatment of a variety of diseases associated with abnormal mitochondrial function.

Abstract: The invention provides the use of selective mGluR5 antagonists for the treatment of pain and anxiety, and the use of mGluR antagonists for the treatment of pain, whereby analgesic effect is achieved by interaction of said antagonists primarily or predominantly at peripheral mGluR receptors.

Abstract: The invention provides compositions and methods for monitoring subcellular compartments such as organelles by energy transfer techniques that do not require specific intermolecular affinity binding events between energy transfer donor and energy transfer acceptor molecules. Provided are methods for assaying cellular membrane potential, including mitochondrial membrane potential, by energy transfer methodologies including fluorescence resonance energy transfer (FRET). Diagnostic and drug screening assays are also provided.