Described are coelenterazine analogues, methods for making the analogues, kits comprising the analogues, and methods of using the compounds for the detection of luminescence in luciferase-based assays.

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.

The invention provides methods and systems for imaging.

In various embodiments methods are provided for identifying a mammal having an elevated risk for an adverse cardiac event (e.g. an MI) and/or determining the prognosis for the mammal. In certain embodiments the methods comprise determining, or causing to be determined, the presence and/or level of antibodies that bind a malondialdehyde acetaldehyde adduct (MAA adduct) in a biological sample from the mammal, where an elevated level of anti-MAA adduct antibodies, as compared to the level found in a normal healthy mammal is an indicator that that said mammal has one or more atherosclerotic lesions and/or is at elevated risk for a myocardial infarction.

The present disclosure provides a genetically modified mouse comprising a genomic nucleic acid encoding human APOE4, a genomic nucleic acid encoding mouse TREM2 modified to include a R47H substitution, and at least one genomic modification selected from the group consisting of: (a) a genomic nucleic acid encoding mouse ABCA7 modified to include an A 1541 G substitution; (b) a genomic nucleic acid encoding mouse APP modified to include G60IR, F606Y, and R609H substitutions; (c) a genomic nucleic acid encoding mouse PLCG2 modified to include a M28L substitution; (d) a genomic nucleic acid encoding mouse MTHFR modified to include a A262V substitution; (e) an inactivated Ceacaml allele; and (f) an inactivated II1rap allele. Methods of producing the genetically modified mouse and methods of using the genetically modified mouse are also provided.

The invention relates generally to polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator (uPA), to activatable antibodies and other larger molecules that include the cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator, and to methods of making and using these polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator in a variety of therapeutic, diagnostic and prophylactic indications.

Provided is an isolated CTLA4 monoclonal antibody. The antibody can highly-specifically bind to CTLA4, and can effectively block the binding of CTLA4 to B7, reduce the activity or expression level of CTLA4, relieve the inhibition of CTLA4 on the immune function of an organism, activate T lymphocytes, and effectively treat tumors and immune system diseases. Also provided are a monoclonal antibody conjugate comprising the pharmaceutical composition and diagnostic composition of the antibody, and the use thereof in the preparation of a drug for preventing and/or treating and/or treating in combination tumors and immune system diseases.

Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include at least one RNA polynucleotides having a open reading reading frame encoding at least varicella zoster virus (VZV) antigen. Methods for preparing and using such vaccines are also described.

Fibroblast activation protein (FAP)-targeting compounds (e.g., conjugates); a method for imaging cancer or fibrosis; and methods for treating an inflammatory disease/disorder and cancer.

The present disclosure relates to genetically modified non-human animals expressing human or chimeric (e.g., humanized) Thrombopoietin (THPO), and methods of use thereof.