Abstract: The present disclosure provides methods and compositions to enhance reprogramming in human cells. In some cases, the method includes contacting human cells with an inhibitor of the TGF? pathway, for example a TGF? receptor (TGF?R) inhibitor in combination with one or more induction factors.

Abstract: The invention encompasses a method for treating a disease or condition mediated by the human MRG-X1 receptor, such as nociception, hyperalgesia, allodynia, pain related to central hypersensitivity conditions, somatic pain, visceral pain, acute pain, chronic pain, post-operative pain, headache, inflammatory pain, neurological pain, musculoskeletal pain, cancer related pain or vascular pain, in a human patient in need thereof comprising administering to the patient a therapeutically effective amount of a 3-substituted-2-(diphenylmethy)-1-azabicyclo[2.2.2]octane or a pharmaceutically acceptable salt thereof. The invention is also directed to the use of these compounds as molecular tools to directly explore the role of the MRG-X1 receptor in pain perception.

Abstract: High-throughput in vitro assays are provided for identifying modulators of transcription activity and RNA expression. New assays, related compositions, apparatus and integrated systems are provided.

Abstract: The invention provides novel methods and compositions for detecting kinase activity in solution, without the use of radioactivity. The methods marry the kinetic advantages of solution-based reaction with the efficiency and high-throughput adaptability of solid-phase wash and detection steps, yet is conveniently practiced in a single tube. The methods may be used to assay for kinase activity per se or, by controlling for the kinase activity, for modulators of kinase activity. The method is exemplified with a preferred chemiluminescent protein kinase assay using biotinylated substrate peptides captured on a streptavidin coated microtiter plate and monoclonal antibodies to detect their phosphorylation.

Abstract: The invention provides promoter specific and promoter non-specific screening assays for identifying an inhibitor of a pathogenic nucleic acid polymerase activity, e.g. an RNA polymerase derived from a pathogenic infectious organism such as a bacterium, protozoan or fungus. Generally, the methods involve forming a mixture of nucleotides, a polynucleotide template, a pathogenic polymerase candidate inhibitor of polymerase activity, where at least one of the nucleotides comprises a detectable label. The mixture is incubated under conditions whereby, but for the presence of the candidate inhibitor, the polymerase transcribes the polynucleotide template by catalyzing the polymerization of the nucleoside triphosphates into a polynucleotide having a nucleotide sequence complementary to that of the polynucleotide template. The nascent transcript is captured by a polynucleotide-selective agent immobilized on a solid substrate for subsequent washing and label detection.

Abstract: Pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene are identified in high throughput drug screening assays. The methods involve combining a labeled transcription factor, a nucleic acid coupled to a ligand, a candidate pharmacological agent and a receptor immobilized on a solid substrate, such as a microtiter plate, filter, or bead. The nucleic acid has at least that portion of a nucleotide sequence naturally involved in the regulation of the transcription of the gene which is necessary for sequence-specific interaction with the transcription factor. The resultant combination is incubated under conditions whereby the receptor is bound to the ligand and, but for the presence of said candidate pharmacological agent, the transcription factor is sequence-specifically bound to the nucleic acid. Unbound transcription factor is then removed or washed from the solid substrate and labelled, sequence-specifically bound transcription factor is detected.