Co-crystals comprising the Nuclear receptor related 1 protein-ligand binding domain (Nurr1-LBD) and a cyclopentenone prostaglandin are provided. Also provided are methods of identifying or designing Nurr1-modulating ligands and compounds based on the crystal structures described herein as well as the applications of said ligands and compounds as Nurr1 modulators or medicaments.

This document provides methods and materials for treating a mammal (e.g., a human) having, or at risk of developing, a proteinopathy. For example, one or more importin polypeptides (and/or nucleic acids designed to express an importin polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy to treat the mammal.

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel nuclear receptors comprising a substitution mutation and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene within a host cell using this inducible gene expression system.

Disclosed herein are methods of treating neurodevelopmental disorders such as schizophrenia (SCZ), bipolar disorder or depression. The methods entail inhibiting expression of miR-219 or overexpressing TLX thereby promoting proliferation of neural stem cells (NSCs) in the subjects.

The present invention encompasses the recognition that an F876L mutation of the androgen receptor (AR) gene confers resistance to the antiandrogens enzalutamide (MDV3100) and ARN-509 and is associated with incidence and/or risk of castration resistant prostate cancer (CRPC). The present invention also provides other AR polypeptide sequences associated with increased incidence and/or risk of CRPC. The present invention also provides screening methods for identification and/or characterization of novel AR polypeptide sequences associated with increased incidence and/or risk of CRPC via exposure to antiandrogens and for identification and/or characterization of agents to treat and/or reduce risk of CRPC by virtue of their effect on AR transcriptional activation.

The present invention describes genomic biomarkers that have been discovered to correlate with varied individual responses (efficacy, adverse effect, and other end points) to therapeutic retinoid X receptor modulator, such as bexarotene, in treating diseases such as, non small cell lung cancer. The newly discovered biomarkers and others in linkage disequilibrium with them can be used in companion diagnostic tests which can help to predict drug responses and apply drugs only to those who will be benefited, or exclude those who might have adverse effects, by the treatment.

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a Group H nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

The present disclosure relates to methods of determining a treatment course of action. In particular, the present disclosure relates to mutations in the gene encoding estrogen receptor and their association with responsiveness to estrogen therapies for cancer.

The present invention is directed to the use of compounds which are modulators of the G protein-Coupled Estrogen Receptor (GPER) for the inhibitionand/or treatment of Bacterial infections, especially including metMctHin-resistant Staphylococcus aureus (MRSA) infections. Pharmaceutical compositions and methods of treatment of bacterial pathogens, including MRSA are also described.

The invention relates to a novel ligand inducible polypeptide coupling system and methods of modulating cell signal transduction pathways and other intracellular and extracellular protein-protein interactions.