Abstract: Disclosed herein are compositions and pharmaceutical formulations comprising a functionally selected B-arrestin-biased NTSR1 ligand (such as SBI-553 and SBI-810) and methods of using those compositions and pharmaceutical formulations for treating and/or preventing pain.

Abstract: Provided are methods for detecting protein interactions in a sample, the methods comprising: (a) detecting two or more polypeptides that when associated emit a first detectable signal in a first light emission spectrum; (b) contacting the two or more polypeptides with a third polypeptide conjugated to a dipole acceptor moiety that has a second light emission spectrum when excited within a light excitation spectrum, wherein the light excitation spectrum overlaps with the first light emission spectrum; and (c) detecting a second detectable signal emitted in the second light emission spectrum by the dipole acceptor moiety. Also provided are bioluminescent complexes comprising: (a) a first polypeptide conjugated to a dipole acceptor moiety, wherein the emits a first detectable signal in a first light emission spectrum.

Abstract: Provided are methods for detecting protein interactions in a sample, the methods comprising: (a) detecting two or more polypeptides that when associated emit a first detectable signal in a first light emission spectrum; (b) contacting the two or more polypeptides with a third polypeptide conjugated to a dipole acceptor moiety that has a second light emission spectrum when excited within a light excitation spectrum, wherein the light excitation spectrum overlaps with the first light emission spectrum; and (c) detecting a second detectable signal emitted in the second light emission spectrum by the dipole acceptor moiety. Also provided are bioluminescent complexes comprising: (a) a first polypeptide conjugated to a dipole acceptor moiety, wherein the emits a first detectable signal in a first light emission spectrum.

Abstract: Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

Abstract: Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

Abstract: Recombinant non-human mammals having reduced or no expression of vesicular acetylcholine transporter protein (VAChT) as compared to the corresponding wild-type mammal are provided. The mammal may have, e.g., impaired performance in object and social recognition and/or impaired neuromuscular performance and/or alterations in autonomic nervous system function as compared to the corresponding wild-type mammal. Methods of screening a compound for cholinergic activity or activity in treating a cholinergic neurotransmission disorder are also provided. In addition, a cell such as a nerve cell isolated from a mammal as described herein is provided, along with cell cultures, which are useful in vitro for screening the activity of candidate compounds for their effect on cholinergic neurotransmission, and for their activity in treating cholinergic neurotransmission disorders.

Abstract: Recombinant or transgenic non-human mammals are described having a mutant tryptophan hydroxylase 2 (Tph2) gene resulting in altered synthesis of 5-hydroxytryptophan and serotonin in the brain. In some embodiments the mutant tryptophan hydroxylase 2 gene contains mouse R439H and/or P447R functional mutations, or their corresponding mutations in other species. Congenic non-human mammals having mutant tryptophan hydroxylase 2 genes are also provided. Methods of screening a compound for serotonergic activity or activity in treating a serotonergic neurotransmission dysregulation disorder are provided, which include administering a test compound to a recombinant non-human mammal and then detecting the presence or absence of serotonergic activity, or activity in treating a serotonergic neurotransmission dysregulation disorder, in the mammal. A cell such as a nerve cell (e.g.

Abstract: A method of treating a subject for Parkinson's disease comprises administering said subject a phenylisopropylamine in an amount effective to treat said Parkinson's disease. In some embodiments the method is used to treat at least a motor symptom of Parkinson's disease; in some embodiments the method is used to treat at least a non-motor symptom of Parkinson's disease.

Abstract: Described are methods of detecting G-protein coupled receptor (GPCR) activity in vivo and in vitro; methods of assaying GPCR activity; and methods of screening for GPCR ligands, G Protein-coupled receptor kinase (GRK) activity, and compounds that interact with components of the GPCR regulatory process.

Abstract: A method of treating a subject for a serotonergic neurotransmission dysregulation disorder, comprises administering the subject a serotonin enhancer (e.g., a serotonin reuptake inhibitor) in an amount effective to treat the disorder; and concurrently administering the subject 5-hydroxytryptophan in an amount effective to enhance the activity of the serotonin enahancer, (e.g., serotonin reuptake inhibitor). In preferred embodiments the disorder is depression, anxiety, or substance abuse.

Abstract: A method of screening a subject for a serotonergic neurotransmission dysregulation disorder comprises detecting the presence or absence of an Tph2 mutation in the subject; and then determining that the subject is at increased risk of a serotonergic neurotransmission dysregulation disorder due to the presence or absence of the Tph2 mutation.

Abstract: A method, system and Edge Multimedia Messaging Service (MMS) Relay/Server for handling MMS messages in an MMS system, wherein incoming MMS messages are received at the Edge MMS Relay/Server from User Agents (UAs). The former determines criteria associated with the MMS messages and based on the criteria, selectively forwards the MMS messages to the proper MMS Relay/Server of a second stage of the MMS system, where the MMS messages are handled based on their type, and further delivered to the MMS recipients. Such criteria may include the retrieval time of the messages, the type of subscription of the user (prepaid vs postpaid), the need for transcoding the MMS message, and immediate vs future delivery time.

Abstract: The present invention relates to methods of treating disease by altering G protein coupled receptor kinase (GRK) 6. This may be done by altering the expression or activity of the protein, for example. The present invention may be used for disease diagnosis, by detecting the expression or activity of GRK6. The present invention relates to a GRK6 deficient mouse, GRK6 splice variants, and methods of use. The present invention also relates to methods of identifying compounds that alter GRK6 activity. The present invention relates to disease treatment by altering GRK6 expression or activity.

Abstract: The present invention relates to compounds that alter GPCR internalization and new methods for their identification. Compounds of this invention include modified phosphoinositide 3-kinase (PI3K), modified HEAT domain, modified ?-adrenergic receptor kinase 1 (?ARK1), as well as other peptides or small molecules that alter GPCR internalization. The present invention also includes the use of such compounds to treat GPCR-related diseases, such as cardiovascular disease, heart failure, asthma, nephrogenic diabetes insipidus, or hypertension.

Abstract: Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protein-coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein ? subunit (mammalian G?). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein ?-subunit (yeast G?). The cells are useful for screening compounds which affect the rate of dissociation of G? from G?? in a cell. Also disclosed is a novel DNA expression vector useful for making cells as described above. The vector contains a first segment comprising at least a fragment of the extreme amino-terminal coding sequence of a yeast G protein-coupled receptor. A second segment is positioned downstream from the first segment (and in correct reading frame therewith), with the second segment comprising a DNA sequence encoding a heterologous G protein-coupled receptor.

Abstract: The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have carboxyl terminal tails comprising one or more sites of phosphorylation, preferably one or more clusters of phosphorylation sites. The modified GPCRs of the present invention may comprise a retained portion of a carboxyl-terminus region from a first GPCR fused to a polypeptide, wherein the polypeptide comprises the one or more clusters of phosphorylation. The present invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRS.

Abstract: A deterring device for deterring unsafe usage of a handrail part of an escalator or other conventional people moving devices. The deterring device includes an elongated body positioned in an overlying yet space relationship relative to the handrail. The body define an overriding surface having a generally concave shaped configuration for allowing intended users to grasp the handrail while blocking access to the handrail by other body parts of the intended users and blocking access to the handrail from the exterior of the people moving device.