As described herein, a hybrid voltage sensor genetically-encoded voltage indicator (GEVI) for mitochondria or endoplasmic reticulum includes a transmembrane domain, and a fluorescent protein, wherein a terminus of the transmembrane domain and a terminus of the fluorescent protein are covalently linked directly or by a linker comprising 1 to 20 amino acids, and wherein the transmembrane domain comprises SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or a peptide with greater than 85%, 90%, 95% or 98% identity to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4. Also described are expression vectors, expression cassettes, and organelle membranes, as well as methods of determining the voltage across an organelle using the GEVIs.

Provided are ion channel antagonists/blockers and uses thereof. Specifically, it provides the compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, preparation method therefor and application thereof. Definition of each group in the formula can be found in the specification for details. Provided is also pharmaceutical composition useful for treatment of heart disease and other ion channel related diseases.

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The invention relates to a method for increasing the lifespan of animal sperm comprising contacting said sperm with an inhibitor of Slo3 potassium channel. The invention also relates to a use of an inhibitor of Slo3 potassium channel, for increasing the lifespan of animal sperm or motility of capacitated animal sperm, comprising contacting an inhibitor of Slo3 potassium channel with said sperm. Moreover, the invention relates to an artificial insemination instrument for use in artificial insemination of an animal, comprising animal sperm in contact with an inhibitor of Slo3 potassium channel. The invention also relates to a method for artificially inseminating an animal using said artificial insemination instrument. Eventually, the invention relates to a method for increasing the fertility of an animal, comprising contacting sperm of said animal with an inhibitor of Slo3 potassium channel; then artificially inseminating said animal with said sperm.

This invention relates to methods of identifying, synthesizing, optimizing and profiling compounds that are inhibitors or activators of proteins, both naturally occurring endogenous proteins as well as certain variant forms of endogenous proteins, and novel methods of identifying such variants. The method accelerates the identification and development of compounds as potential therapeutically effective drugs by simplifying the pharmaceutical discovery and creation process through improvements in hit identification, lead optimization, biological profiling, and rapid elimination of toxic compounds. Implementation results in overall cost reductions in the drug discovery process resulting from the corresponding increases in efficiency.

The present invention relates to a method for screening an inhibitor of ATP11C or CDC50A, comprising determining (a) exposure of phosphatidylserine on cell surface, (b) engulfment of cells by macrophages, or (c) cleavage of ATP11C by caspase. The present invention also relates to a method for inducing engulfment of cells by macrophages, comprising inhibiting ATP11C or CDC50A.

The present invention relates to a method for quantifying a therapeutic antibody in a sample of a human individual comprising a step of adding to a test sample which may contain therapeutic antibodies to be quantified a known amount of two or more labeled forms of said therapeutic antibodies.

The invention, in some aspects relates to light-activated ion channel molecules and methods for their use to alter cell activity and function. Light-activated ion channel molecules of the invention can be administered to subjects, expressed in cells, and activated with light, to alter membrane potential in the cells, and can be used in methods for assaying compounds, treating diseases and conditions, compound screening and more.

This disclosure provides a multimeric hepatitis B virus (HBV) protein binding molecule, e.g., a dimeric IgA or a pentameric or hexameric IgM binding molecule, comprising at least two bivalent binding units, or variants or fragments thereof, each comprising at least two antibody heavy chain constant regions or fragments thereof, wherein each heavy chain constant region or fragment thereof is associated with an HBV antigen binding domain. The disclosure also provides compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules.

The present invention is directed to a mammalian-avian chimeric model system comprising a fertilized avian egg comprising a chorioallantoic membrane (CAM); and multiple types of mammalian cells dispersed in a hydrogel. Further provided is a method for preparing the system and a method of using the same.

Described in certain example embodiments herein are systems, methods, and uses thereof for high-throughput in vitro evaluating multiple test compounds in parallel for biological or pharmacological functions. In certain embodiments, the system allows the selection of a subset of test compounds from a group of test compounds to form an optimized pool, and methods are provided to use such optimized pool of test compounds to identify and validate therapeutic agents for treating diseases and driving guided differentiation of stem cells into desired types of cells. The systems described herein can provide, for example, a cost-effective and high-quality high-throughput approach for drug screening.