The present disclosure provides systems, methods, and devices for the simultaneous determination of a single cell's response to a stimuli and characterization of its cell response. The present disclosure further provides methods for detection of disease state, clinical management of a subject suffering from a disease, drug screening, prediction of drug response, and stands to help direct drug and diagnostic development for the treatment of disease.

This disclosure relates to the discovery that a G12V mutant of KRAS (hereinafter KRAS G12V) binds to JAK1, i.e., the existence of a KRAS G12V and JAK1 binding interaction. In certain embodiments, this disclosure relates to methods of disrupting the KRAS G12V and JAK1 interaction reversing KRAS G12V induced immune escape by cancer cells utilizing agents that prevent the binding of JAK1 to KRAS G12V.

Methods of treating subjects with atopic dermatitis, e.g., associated with mutations in the TMEM79 gene, using Wnt inhibitors, e.g., porcupine inhibitors.

Embodiments of the invention are directed of compositions for activation or inhibition of the Octβ2 receptor and uses thereof. The inventors have discovered that the beta adrenergic-like octopamine receptor Octβ2 serves as a key signaling molecule for ovulation and recruits protein kinase A and Ca2+/calmodulin-sensitive kinase II as downstream effectors for this activity. Octβ2R homozygous mutant females are sterile, and display normal courtship, copulation, sperm storage and post-mating rejection behavior but were unable to lay eggs.

Fluorescent probe compounds comprising fluorescent cholic acid derivative are used for visualizing the influence of a candidate compound on biliary excretion in in vitro or in vivo biological models, including certain probes developed report on the activity of the bile salt export pump (BSEP). Visualization is done on hepatocyte cultures with formed bile canaliculi or on liver systems that are exposed to the fluorescent probes and the candidate compound. Visualization is done by fluorescence microscopy. The probes are particularly suitable for early screening of multiple candidate compounds.

Newly identified mammalian taste-cell-specific G protein-coupled receptors which function as hetero-oligomeric complexes in the sweet taste transduction pathway, and the genes and cDNA encoding said receptors are described. Specifically, T1R G protein-coupled receptors active in sweet taste signaling as hetero-oligomeric complexes, 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 identifying putative taste modulating compounds using such hetero-oligomeric complexes also described, as is a novel surface expression facilitating peptide useful for targeting integral plasma membrane proteins to the surface of a cell.

The present invention pertains to an N-terminally truncated interleukin (IL)-38 protein, or functional variants thereof, as well as to nucleic acids and vectors encoding the truncated IL-38 peptide and recombinant cells comprising these nucleic acids or vectors. The invention shows that IL-38 is N-terminally processed and that the truncated version of the cytokine acts as an antagonist of immune activation in macrophages. This indicates a use of the truncated cytokine in the treatment and prevention of autoimmune disorders. The invention further provides pharmaceutical compositions comprising the truncated IL-38 protein, and method for screening modulators of the function of truncated IL-38.

The present invention pertains to fields of biochemistry and molecular biology, relates to an αO-superfamily conotoxin peptide, pharmaceutical composition thereof, preparation method and use thereof. The present invention further relates to a propeptide of the conotoxin peptide, nucleic acid construct thereof, expression vector and transformed cell thereof, and fusion protein thereof. The present invention further relates to a method for blocking acetylcholine receptors as well as a use of the conotoxin peptide in the manufacture of a medicament. The new αO-superfamily conotoxin peptide of the present invention is capable of specifically blocking acetylcholine receptor (nAChRs) (e.g., α9α10 nAChR), and NMDA receptor (e.g., NR2C NMDAR), and has activity for treatment of neuralgia, addiction, and activity for treatment of chemotherapy of cancers, breast cancer, lung cancer, wound healing, epilepsia, ischemia, and thus is promising in the manufacture of analgesic, a medicament for treatment of addiction, and a tool drug for neuroscience.

The invention features therapeutic compositions comprising agents useful for the treatment or prevention of pruritis, and methods useful for identifying such agents.

The invention provides nucleic acid and amino acid sequences for a novel family of taste transduction G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of taste transduction G-protein coupled receptors.