Provided herein are methods of treating hypercalcemia in a subject, comprising administering to the subject a therapeutically effective amount of a composition that decreases the expression level and/or activity of GPR64. Compositions comprising the therapeutic agents and methods of screening for agonists and inhibitors of GPR64 are also provided. Compositions and methods for treating primary hyperparathyroidism, secondary hyperparathyroidism, hypoparathyroidism, and osteoporosis without hyperparathyroidism are also provided.

There is disclosed a molecular composition(s) of a novel tissue protective erythropoietin (EPO) binding receptor protein complex, termed NEPOR. Presence of NEPOR components on a tumour allows EPO to impinge on the survival of associated cells thereby enhancing tumour progression and negatively effecting patient survival. Presence of NEPOR represents a prognostic biomarker for poorer patient outcome. Thus, methods are provided for stratifying patients having a tumour as suitable (i.e. NEPOR not present) or non-suitable (i.e., NEPOR present) for EPO treatment, comprising: (a) isolating a tissue sample from an individual who is receiving or is a candidate for receiving erythropoietin, (b) determining the level of expression of the NEPOR gene(s) (mRNA) and/or the presence of the NEPOR gene product (protein) from the isolated tissue, and (c) correlating the presence of an NEPOR gene expression product or the presence of NEPOR protein to a physiological response to the treatment with erythropoietin. Furthermore, by disclosing the molecular compositions of NEPOR species, there are disclosed methods for rationally identifying/designing NEPOR modulating therapeutics. Methods also are provided for treating neurological insults such as stroke (via enhancement of NEPOR activity) and cancer (via down-regulation of cyto-protective signaling from NEPOR).

The present technology is directed to compounds, compositions, and methods related to non-morphinan-like mu opioid receptor agonists. Compounds of the present technology demonstrate remarkable potency and selectivity for the mu opioid receptor over the kappa opioid receptor, while also exhibiting a significant reduction (or, essentially, absence) of the negative side effects of many morphine-derived compounds.

A power-management unit is described. This power-management unit allows a common signal line to communicate data between an integrated circuit (which may be external to the power-management unit) and a battery-monitoring mechanism in a battery pack, and to convey a signal that represents a temperature state of the battery pack to a temperature-monitoring circuit or mechanism that monitors the temperature state of the battery pack. In particular, the power-management unit may include a single-wire interface or a multiplexer that, at a given time, selectively couples the signal line from the battery pack either to the integrated circuit or the temperature-monitoring circuit based on a control signal provided by the integrated circuit (for example, via an I2C bus or interface). In this way, the power-management unit may reduce the number of signal lines needed to communicate with the battery-monitoring mechanism and to convey the signal.

The invention provides methods and compositions for the diagnosis, prognosis, and/or treatment response characterization of individuals suffering from systemic lupus erythematosus (SLE) using single cell network profiling.

Newly identified mammalian taste-cell-specific G protein-coupled receptors, and the genes and cDNA encoding said receptors are described. Specifically, T1R G protein-coupled receptors active in taste signaling, and the genes and cDNA encoding the same, are described, along with methods for isolating such genes and for isolating and expressing such receptors. Methods for representing taste perception of a particular taste stimulus in a mammal are also described, as are methods for generating novel molecules or combinations of molecules that elicit a predetermined taste perception in a mammal, and methods for simulating one or more tastes. Further, methods for stimulating or blocking taste perception in a mammal are also disclosed.

In cancers such as prostate cancer, the combination of PTEN loss and activation of Myc activates an adaptive stress response that enables tumor cells to escape the stress of massively upregulated protein synthesis. This pro-survival response is mediated by the PERK-phosphorylated eIF2α axis of the UPR adaptive response. Agents that disrupt PERK-eIF2α pathways disrupt the adaptive response and lead to cancer cell death from uncontrolled growth. For example, ISRIB and derivatives may be employed as therapeutic agents to disrupt PERK-mediated adaptive mechanisms. Additionally PTEN loss and activation of Myc provides a diagnostic marker that enables better prognosis and the selection of amenable treatments.

The invention provides methods, compositions, and systems for diagnosis, prognosis, evaluation of status, and/or determination of treatment for pathological conditions.

Genetically encoded calcium indicator (GECI) polypeptides and the nucleic acid molecules encoding such polypeptides are provided. In addition, methods of using such nucleic acids and polypeptides in methods of screening for agonists or antagonists of G-protein coupled receptor (GPCR) or ion channels and methods of monitoring neural activity also are provided.

The present invention relates to methods of treating or preventing respiratory infections, in particular respiratory infections in patients with an underlying respiratory disorder such as chronic obstructive pulmonary disease (COPD). The present invention also relates to methods of treating or preventing COPD or COPD exacerbations. The invention particularly describes the role of Notch 3 and/or Notch 4 signalling in such methods and the use of Notch 3 and/or Notch 4 as therapeutic and screening targets.