This document relates to non-human animal models (e.g., non-human mammalian models such as mouse models) for aging (e.g., neural aging). For example, non-human animal models having reduced or eliminated levels of aralkylamine N-acetyltransferase (AANAT) polypeptide expression are provided.

A method for screening an active ingredient of a saltiness enhancer, the screening method including the following steps: (i) a step for determining whether a test substance is a compound capable of promoting functional expression of the TMC4 gene or TMC4 protein; and (ii) a step for selecting, as an active ingredient of a saltiness enhancer, a test substance that has been determined in step (i) to be a compound capable of promoting functional expression of the TMC4 gene or TMC4 protein.

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 invention is in the field of therapy of gut inflammatory diseases such as Inflammatory Bowel Diseases (IBD) or Irritable Bowel Syndrome (IBS) including Gluten hypersensitivity. The inventors showed that ELA2A secreted by epithelial cells in the extracellular space is over-expressed in IBD conditions degrading tight junction proteins and controlling cytokines expression. Overexpression of ELA2A conferred a pro-inflammatory phenotype both in cell expression systems and in vivo in animal model of IBD. The inventors also showed that ELA2 over-expressing intestinal epithelial cells increase the release of CXCL8 protein compared to control cells. The increased CXCL-8 protein release observed in cells overexpressing ELA2A is inhibited by ELAFIN addition to the culture, in a dose-dependent manner. In particular, the invention relates to inhibitors of Elastase ELA2A, for use in the treatment of Inflammatory Bowel Diseases, such as Crohn's Disease, Ulcerative Colitis, Celiac disease, and Pouchitis.

Based on the discovery that MBLAC1 is a specific, high-affinity target for Ceftriaxone (Cef), MBLAC1 may be used for identifying treatments for addiction to substances of abuse. Methods for identifying therapeutic agents for treatment of addiction to a substance of abuse include using an assay to determine if a test agent is capable of binding to MBLAC1 or disrupting binding between MBLAC1 protein and Cef, and identifying such a test agent as a candidate therapeutic agent for treatment of addiction to a substance of abuse. MBLAC knock-out (KO) animals, methods of use thereof, and kits are used for identifying a therapeutic agent that reduces the actions of at least one substance of abuse. Methods also include using cellular extracts from tissue or cultured cells taken from wild-type (WT) MBLAC1 and MBLAC1 KO animals for screening for novel, Cef-like molecules in vitro, and using cells from a MBLAC1 KO animal to test for Cef-like actions of a test molecule.

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Disclosed is a method of detecting synergistic drug combinations for the treatment of a cancer, comprising: culturing infected cells in a chamber: contacting the cells in with a first active agent; measuring and/or estimating the concentration of the first active agent at a first and second time point; capturing a first and second optical signal from the contacted cells at the first and second time points; analyzing the first optical signal and the second optical signal to detect cell membrane motion of the cells; analyzing the cell membrane motion to quantify the viability of the cells following contact with the first active agent thereby detecting the drug induced damage at the second time point; measuring, calculating, and/or estimating the repair rate of the cells, therapeutic threshold, rate of sensitivity of therapy, and/or clonal composition of the tumor; repeating said steps with a second active agent.

The present invention provides methods for assessing a compound's potential toxicity.

The present disclosure provides a method and a platform for enhancing detection activity of an interaction between a spike protein receptor binding domain of coronavirus from a specimen and a human angiotensin-converting enzyme II. The method and the platform of the present disclosure use a cleavable luciferase as a report test for the combination of the spike protein receptor binding domain of coronavirus (such as novel coronavirus) and angiotensin-converting enzyme II. Screening is carried out at the cellular level. The strength of the drug's influence on the interaction between the two molecules can be judged by the strength of the luminescence signal. The detection time can be completed within 20 minutes.

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.