Abstract: The current disclosure provides for methods for differentiating stem and progenitor cells into neural cells through an approach that excludes the use of SMAD or Noggin inhibition. Aspects of the disclosure relate to a method for differentiating stem or progenitor cells into neural cells, the method comprising contacting the cells with a compound selected from DMH1, DMH2, K02288, A8301, or combinations thereof.

Abstract: Provided herein are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

Abstract: Chimeric antigen receptor (CAR) bridging protein are provided comprising a CAR-binding domain linked to an antigen-binding domain, which can be used to re-direct the targeting of CAR-T cells. The bridging protein may comprie an antigen-binding domain that targets any antigen of interest, such as, for example, a tumor antigen or viral antigen. Also provided are methods of using the bridging proteins in combination with CAR-T cells to treat a disease, such as, for example, a cancer or an infectious disease.

Abstract: The present disclosure relates to miRNA expression constructs, such as for expression of multiple miRNAs and use thereof to knockdown target gene expression. In some aspects, the expression constructs include a promoter element, a spacer sequence and a miRNA coding sequence. In some aspects, constructs provide enhanced immune cell function.

Abstract: The present disclosure relates to miRNA expression constructs, such as for expression of multiple miRNAs and use thereof to knockdown target gene expression. In some aspects, the expression constructs include a promoter element, a spacer sequence and a miRNA coding sequence. In some aspects, constructs provide enhanced immune cell function.

Abstract: Provided herein are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

Abstract: The present invention is directed to tissue substitute materials and uses thereof useful for the treatment of wound, skin wounds and in particular chronic ulcers. The invention further relates to methods of preparation of those tissue substitute materials.

Abstract: Provided herein are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

Abstract: The present disclosure relates to miRNA expression constructs, such as for expression of multiple miRNAs and use thereof to knockdown target gene expression. In some aspects, the expression constructs include a promoter element, a spacer sequence and a miRNA coding sequence. In some aspects, constructs provide enhanced immune cell function.

Abstract: Disclosed are methods for producing a clonal population of cells involving: a) obtaining a population of pluripotent or multipotent cells that have been expanded in vitro and maintained in an undifferentiated or essentially undifferentiated state; b) expanding individualized cells of the population into clonal populations of cells; and c) selecting one or more clonal population of cells determined to have the ability to differentiate into a population that is at least about 50% homogeneous for either neural cell types, hepatocytes, or cardiomyocytes. Also disclosed are clonal populations of cells produced by the methods of the present invention, and methods of treating disease in subjects involving administration of clonal cells of the present invention to a subject. Methods of screening test compounds that involve contacting a test compound with a clonal population of cells produced by the methods of the present invention are also set forth.

Abstract: Provided herein are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

Abstract: Provided herein are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

Abstract: This invention relates to a method of identifying a modulator of an NADPH oxidase, whereby said modulator is suitable as a lead compound and/or as a medicament for the treatment and/or prevention of hearing loss and/or phantom hearing, the method comprising the steps of (a) contacting a test compound with a protein, wherein said protein (i) comprises or consists of the amino acid sequence of any one of SEQ ID NO: 1, 3 or 5, or (ii) is encoded by a nucleic acid comprising or consisting of the sequence of any one of SEQ ID NO: 2, 4, 6, 23 or 24, or (iii) is a fragment of the protein according to (i) or (ii) and exhibits NADPH oxidase activity, or (iv) has a sequence at least 75% identical with the protein according to (i) or (ii) or with the fragment according to (iii) and exhibits NADPH oxidase activity, and optionally with one or more NADPH oxidase subunits, under conditions allowing binding of said test compound to said protein or, if present, said subunit(s); (b) optionally determining whether said test com

Abstract: Recombinant nucleic acid molecules are provided that form hair pin structures and can be used to down-regulate gene expression. For example, a nucleic acid molecule can comprise a flanking and lower stem loop sequence from a mir-16 gene; an antisense target sequence; a mir-30 loop sequence; a complement of the anti-sense target sequence; and a lower stem loop complementary to the mir-16 sequence. Methods for down regulating gene expression in a cell using such recombinant nucleic acid molecules are also provided.

Abstract: Methods for selecting transgenic cells comprising two or more drug resistance genes with a combination of cytotoxic drugs (e.g., trimetrexate (TMTX) and hydroxyurea (HU)). Such selection can be completed in vitro or in vivo. Transgenic cells and vectors comprising combinations of resistance genes are also provided. Transgenic cells of the embodiments can be used as cell based therapeutics, such as for treatment of HIV infection.

Abstract: Recombinant nucleic acid molecules are provided that form hair pin structures and can be used to down-regulate gene expression. For example, a nucleic acid molecule can comprise a flanking and lower stem loop sequence from a mir-16 gene; an antisense target sequence; a mir-30 loop sequence; a complement of the anti-sense target sequence; and a lower stem loop complementary to the mir-16 sequence. Methods for down regulating gene expression in a cell using such recombinant nucleic acid molecules are also provided.

Abstract: This invention relates to a method of identifying a modulator of an NADPH oxidase, whereby said modulator is suitable as a lead compound and/or as a medicament for the treatment and/or prevention of hearing loss and/or phantom hearing, the method comprising the steps of (a) contacting a test compound with a protein, wherein said protein (i) comprises or consists of the amino acid sequence of any one of SEQ ID NO: 1, 3 or 5, or (ii) is encoded by a nucleic acid comprising or consisting of the sequence of any one of SEQ ID NO: 2, 4, 6, 23 or 24, or (iii) is a fragment of the protein according to (i) or (ii) and exhibits NADPH oxidase activity, or (iv) has a sequence at least 75% identical with the protein according to (i) or (ii) or with the fragment according to (iii) and exhibits NADPH oxidase activity, and optionally with one or more NADPH oxidase subunits, under conditions allowing binding of said test compound to said protein or, if present, said subunit(s); (b) optionally determining whether said test com

Abstract: A method of differentiation stem cells cells by contacting stem cells with a dopaminergic differentiation agent is provided in certain aspects. For example, the agent may comprise substituted benzoxazole. These methods and compositions may be used in toxicological screens, e.g., to evaluate the neurotoxicity of a test compound or treatment of neurological disorders.

Abstract: This invention relates to modulators of NADPH oxidase as a medicament for the treatment and/or prevention of hearing loss and/or phantom hearing. Such modulators preferably act by inhibiting NADPH oxidase activity, wherein the NADPH oxidase comprises or consists of the amino acid sequence of any one of SEQ ID NO: 1, 3 or 5, or (ii) is encoded by a nucleic acid comprising or consisting of the sequence of any one of SEQ ID NO: 2, 4, 6, 23 or 24, or (iii) is a fragment of the protein according to (i) or (ii) and exhibits NADPH oxidase activity, or (iv) has a sequence at least 75% identical with the protein according to (i) or (ii) or with the fragment according to (iii) and exhibits NADPH oxidase activity. Also provided are pharmaceutical compositions, medical uses and diagnostic uses of compounds of the invention.

Abstract: A method of preparing neural precursor cells by exposing pluripotent stem cells or neural stem cells to a differentiation agent. The agent is a pyridine analog, which in preferred embodiments is a phenylethynyl-substituted or phenylazo-substituted pyridine. In other embodiments, a method of enhancing neural precursor cell survival is provided in which the survival is enhanced by exposure to the pyridine analog. In further embodiments, a method of preparing neuronal cells is provided in which pluripotent or neural stem cells exposed to the pyridine analog are then incubated without the pyridine analog, resulting in differentiation into neurons, astrocytes and oligodendrocytes. These methods may be used in toxicological screens, e.g., to evaluate the neurotoxicity of a test compound.