The invention relates to compounds that specifically bind a T1R1/T1R3 or T1R2/T1R3 receptor or fragments or sub-units thereof. The present invention also relates to the use of hetero-oligomeric and chimeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli. Further, the invention relates to the constitutive of cell lines that stably or transiently co-express a combination of T1R1 and T1R3; or T1R2 and T1R3; under constitutive or inducible conditions. The use of these cells lines in cell-based assays to identify umami and sweet taste modulatory compounds is also provided, particularly high throughput screening assays that detect receptor activity by use of fluorometric imaging.

The invention relates to compounds that specifically bind a T1R1/T1R3 or T1R2/T1R3 receptor or fragments or sub-units thereof. The present invention also relates to the use of hetero-oligomeric and chimeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli. Further, the invention relates to the constitutive of cell lines that stably or transiently co-express a combination of T1R1 and T1R3; or T1R2 and T1R3; under constitutive or inducible conditions. The use of these cells lines in cell-based assays to identify umami and sweet taste modulatory compounds is also provided, particularly high throughput screening assays that detect receptor activity by use of fluorometric imaging.

The present invention relates to methods, monitors and systems, useful, for example, for advanced detection of sepsis in a subject.

The present invention relates to methods, monitors and systems, useful, for example, for advanced detection of sepsis in a subject.

The invention provides methods for identifying protein modulators (e.g., antibody agonists) of eukaryotic cells. The methods typically involve expressing a combinatorial agent library (e.g., via lentiviral vectors) inside a eukaryotic cell type (e.g., a mammalian cell) and then directly selecting for agents (e.g., antibodies) that are agonist of a target molecule (e.g., a signaling receptor) that modulates a phenotype of or elicits a cellular response in the cell. Some related methods involve co-culturing a cell expressing a combinatorial agent library and a second cell, and then selecting agents that modulate a phenotype of or elicit a cellular response in the second cell. Preferably, the agents are antibodies and are introduced into and expressed in the starting cells under conditions each individual cell expresses no more than 3 different members of the antibody library. In addition, the invention provides methods for identifying protein agonists that capable of reprograming or trans-differentiating a target cell. Also provided in the invention are specific agonist antibodies of signaling receptors or biomolecules that modulate a phenotype or effectuate a cellular response in a eukaryotic cell (e.g., agonist antibodies of EpoR, TpoR or G-CSFR). Further provided in the invention are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

The screening method of the present invention is useful for screening drugs such as insulin secretagogues having an insulin secretagogue activity with minimized side effects (hypoglycemia induction, etc.). The transformant in which a polynucleotide encoding the fusion protein used for the screening method is introduced, the screening kit comprising the transformant, etc. are also useful for screening excellent drugs.

The screening method of the present invention is useful for screening drugs such as insulin secretagogues having an insulin secretagogue activity with minimized side effects (hypoglycemia induction, etc.). The transformant in which a polynucleotide encoding the fusion protein used for the screening method is introduced, the screening kit comprising the transformant, etc. are also useful for screening excellent drugs.

The present disclosure provides methods and compositions that find use in facilitating a diagnosis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in a subject. The methods and compositions involve measurement of at least one of proteins: IL-16, IL-7, VEGF, CXCL9, CX3CL1, CCL24, CCL19, and CCL11 in a body fluid sample of a subject suspected of having CFS/ME. Levels of one or more of the aforementioned proteins can be used to facilitate a diagnosis of a CFS/ME and/or confirm a diagnosis of CFS/ME. The methods and compositions of the present disclosure also find use in screening subjects for clinical trials and facilitating treatment decisions for a subject.

The present disclosure provides methods and compositions that find use in facilitating a diagnosis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in a subject. The methods and compositions involve measurement of at least one of proteins: IL-16, IL-7, VEGF, CXCL9, CX3CL1, CCL24, CCL19, and CCL11 in a body fluid sample of a subject suspected of having CFS/ME. Levels of one or more of the aforementioned proteins can be used to facilitate a diagnosis of a CFS/ME and/or confirm a diagnosis of CFS/ME. The methods and compositions of the present disclosure also find use in screening subjects for clinical trials and facilitating treatment decisions for a subject.

Improved methods and systems for diagnosing and for treating Cushing's syndrome and Cushing's Disease are provided herein, including methods and systems for concurrently treating Cushing's syndrome and differentially diagnosing Cushing's Disease from Ectopic Cushing's Syndrome in a patient with an established diagnosis of ACTH-dependent Cushing's syndrome. Treatment methods can use glucocorticoid receptor antagonists (GRAs), which differentially affect the ratio of cortisol to ACTH levels in patients having Cushing's Disease versus patients having Ectopic Cushing's Syndrome. Methods for concurrently treating and differentially diagnosing Cushing's Disease from Ectopic Cushing's Syndrome include obtaining baseline cortisol and ACTH levels of a patient, treating the patient with a GRA according to a protocol that would typically substantially elevate cortisol levels, obtaining post-treatment cortisol and ACTH levels of the patient, determining a differential relationship between baseline cortisol and ACTH levels and post-treatment cortisol and ACTH levels and providing a positive diagnosis based on the differential relationship.