Abstract: Apelin receptor modulators can improve physical performance, slow progression of age-related frailty, and can reduce age-related muscle weakness in human patients. This disclosure provides methods for treating muscle conditions using a particular class of apelin receptor modulators (e.g., agonists). The muscle condition can be an age-related muscle condition. Also provided is a method for maintaining and/or increasing muscle mass, muscle function, and/or muscle strength in an elderly subject by administration of the apelin receptor modulator. In some embodiments, the apelin receptor modulator (e.g., agonist) is BGE-105, or a pharmaceutically acceptable salt thereof.

Abstract: The present invention is directed to antibodies and antigen binding fragments thereof having binding specificity for PACAP. The antibodies and antigen binding fragments thereof comprise the sequences of the VH, VL, and CDR polypeptides described herein, and the polynucleotides encoding them. Antibodies and antigen binding fragments described herein bind to and/or compete for binding to the same linear or conformational epitope(s) on human PACAP as an anti-PACAP antibody. The invention contemplates conjugates of anti-PACAP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. Methods of making said anti-PACAP antibodies and antigen binding fragments thereof are also contemplated.

Abstract: The methods and compositions described herein relate to producing, expanding, enriching, and/or maintaining hematopoietic stem cells ex vivo by treating the cells with an agent(s) that exhibits two or more activities selected from modulation of histone methylation; inhibition of TGF? signaling; inhibition of p38 signaling; activation of canonical Wnt signaling; and modulation of histone acetylation. In some embodiments, the technology described herein relates to transplantation of hematopoietic stem cells.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize hedgehog activity.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention relates to a stable pluripotent reprogrammed cells, and compositions and methods of isolation and uses thereof, wherein the stable pluripotent reprogrammed cells is derived from a somatic cell and has undergone incomplete remodeling of the epigenome. In some embodiments, the stable reprogrammed cell is a human stable reprogrammed cell. In some embodiments, the stable reprogrammed cell has a statistically significant lower level of expression of one or any combination of Nanog, Dnmt3b, Lefty2 as compared to an induced pluripotent stem cell. In some embodiments, the stable reprogrammed cell has a statistically significant higher level of expression of one or any combination of Tdgf1, Tert or endogenous Sox2 as compared to a somatic cell from which it was derived. In some embodiments, the stable reprogrammed cell has a statistically significant faster rate of doubling as compared to an induced pluripotent stem cell (iPSC) or an embryonic stem (ES) cell.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The disclosure features a method of producing a reprogrammed cell (e.g. an induced pluripotent stem cell or an undifferentiated cell) from a differentiated (e.g. somatic) cell. In some embodiments, the methods includes contacting a differentiated (e.g. somatic cell) with a TGFBR1 inhibitor or anti-TGF-?-antibody to produce a reprogrammed cell (e.g. pluripotent stem cell or undifferentiated cell). Embodiments of the present invention relate to a reprogrammed cell and methods and compositions for producing a chemically produced reprogrammed cell or populations thereof.

Abstract: Methods, compounds and compositions for promoting motor neuron survival and the treatment of a neurodegenerative disorders such as Spinal Muscular Atrophy (SMA) are described herein.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize hedgehog activity.

Abstract: A light weight soft fly case for holding fishing flies that can be clipped on or removed via an integrated rotatable clip, to a belt, harness, suspender or pocket that makes them readily accessible with one hand to the fisherman. The light weight soft fly case would be rectangular in shape, be made from nylon and neoprene, with a one piece case construction, and with a one handed hook and loop closure. The light weight soft fly case would include a nylon gusset hinge limiting the opening to a 90 degree angle for easy fly selection. The light weight soft fly case would include an attached but removable ripple foam insert for providing a surface upon which fishing flies might be secured. The light weight soft fly case may include a transparent cover for easy fly identification.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention provides compositions and method for the treatment of spinal muscular atrophy comprising administering a therapeutically effective amount of a therapeutically amount of at least one proteasome inhibitor to a subject in need of treatment of spinal muscular atrophy.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize hedgehog activity.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention relates to a substantially pure population of viable pancreatic progenitor cells, and methods for isolating such cells. The present invention further concerns certain therapeutic uses for such progenitor cells, and their progeny.

Abstract: The present invention relates to a substantially pure population of viable pancreatic progenitor cells, and methods for isolating such cells. The present invention further concerns certain therapeutic uses for such progenitor cells, and their progeny.

Abstract: The present invention concerns the methods and compositions for treating depression and other behavioral and/or emotional disorders of the central nervous system by administering an agonist of hedgehog signaling. Other disorders amenable to treatment by the subject method include attention deficit hyperactive disorders, non-Alzheimer dementia, and various symptoms of memory loss. The present invention also concerns the methods and compositions for enhancing memory and/or cognitive functions, both in a patient suffering from ailment affecting these functions, and in a subject with no diagnosed deficit in memory or cognitive function. The methods and compositions of the present invention stimulate neurogenesis and differentiation, and enhance synaptic transmission of neurons.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity.