Abstract: Disclosed herein are compositions and methods useful for controlling ?-amyloid levels. In particular, the instant invention relates to an antibody that catalyzes hydrolysis of ?-amyloid at a predetermined amide linkage are provided. The present invention also provides a vectorized antibody that is capable of crossing the blood brain barrier and is also capable of catalyzing the hydrolysis of ?-amyloid at a predetermined amide linkage. Also provided are methods for modulating ?-amyloid levels in vivo using antibodies that bind to ?-amyloid. These compositions and methods have therapeutic applications, including the treatment of Alzheimer's disease.

Abstract: Embodied herein are methods of reprogramming somatic cells or tissue stem cells to a more multipotent state or even a pluripotent state, the methods do not involve gene transfer of master transcription factor genes/proteins. The methods are also useful for rapid and efficient cloning of induced pluripotent stem cells after gene transfer of master transcription factor genes/proteins.

Abstract: Disclosed herein are compositions and methods useful for controlling ?-amyloid levels. In particular, the instant invention relates to an antibody that catalyzes hydrolysis of ?-amyloid at a predetermined amide linkage are provided. The present invention also provides a vectorized antibody that is capable of crossing the blood brain barrier and is also capable of catalyzing the hydrolysis of ?-amyloid at a predetermined amide linkage. Also provided are methods for modulating ?-amyloid levels in vivo using antibodies that bind to ?-amyloid. These compositions and methods have therapeutic applications, including the treatment of Alzheimer's disease.

Abstract: This invention provides methods of determining the number and percent of tissue specific stem cells (TSSCs) in a sample of cells, a population of cells or a sample of tissue. The methods rely on detecting the pattern-specific asymmetric localization of asymmetric self-renewal associated (ASRA) proteins or cell cycle specific proteins (CSSP) in cell undergoing asymmetrical self-renewal, which is a characteristic of TSSCs. The methods can be applied to any situations in which the percent of TSSC is desired such as laboratory research on adult stem cells, in drug development tests, prognostic indicator and therapeutic index, as a diagnostic and prognostic indicator and in monitoring TSSC expansion, e.g., in cell manufacturing processes.

Abstract: Embodied herein are methods of reprogramming somatic cells or tissue stem cells to a more multipotent state or even a pluripotent state, the methods do not involve gene transfer of master transcription factor genes/proteins. The methods are also useful for rapid and efficient cloning of induced pluripotent stem cells after gene transfer of master transcription factor genes/proteins.

Abstract: Disclosed herein are peptides comprising a leptin sequence and methods for their use in preventing ObR signaling in a leptin-responsive cell. A leptin peptide of the present invention binds to but does not activate ObR signaling in a leptin-responsive cell, thereby inhibiting the up-regulatory effects of leptin on ObR signaling in the leptin-responsive cell. Administration of the peptide effectively prevents embryo implantation in a mammal to which the peptide has been administered. Also disclosed herein is a method for identifying a peptide antagonist of ObR, wherein the peptide comprises a leptin sequence.

Abstract: Methods and compositions for inhibiting FGF signaling are described. Methods of the invention include contacting an FGF-responsive cell with exogenous heparan sulfate 6-O endosulfatase (Sulf1) in an amount effective to modify endogenous heparan sulfate, thereby inhibiting FGF signaling. Methods of the invention also include contacting an FGF-responsive cell with an exogenous Sulf1-modified compound, the exogenous Sulf1-modified compound being characterized by the ability to reduce binding of FGF2 or FGF4 to FGFR1. Compositions comprising exogenous Sulf1-modified compounds are also provided for use in conjunction with methods of the present invention.

Abstract: Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a ?-amyloid epitope. Also disclosed are methods for inhibiting the formation of ?-amyloid plaques in the brain of a human, or promoting the disaggregation of a preformed ?-amyloid plaque. Such methods recite the administration of a bispecific antibody.

Abstract: Provided is a simple and safe immunization procedure to reduce cancer incidence and increase longevity by modulating IGF-1 levels in the body. Described are cancer preventive vaccines and methods that elicit circulating antibodies specific to insulin-like growth factor 1 (IGF-1) in the body. Many cancers will be less likely to occur and spread in the absence or reduced levels of the stimulatory signals provided by IGF-1. Longevity also can be extended by immunologically lowering the level of bioavailable IGF-1 in adult animals. This prolongation of lifespan resulting from lower IGF-1 levels is produced independently of the inhibitory effects on carcinogenesis. However, the two IGF-1-mediated processes are linked mechanistically. Methods of active and passive immunization to suppress IGF-1 activity are included.

Abstract: Provided herein are methods relating to inhibition of PUMA function for preventing or reducing myocardial cell death. A method for preventing or reducing ischemia/reperfusion induced myocardial cell death in a human is provided as are methods for identifying pharmaceuticals which interfere with PUMA function. Also herein provided is a method for reducing stem cell death in stem cell explants wherein the explants are intended to restore cardiac efficiency following cell death in response to coronary infarct.

Abstract: Disclosed herein are peptides comprising a leptin sequence and methods for their use in preventing ObR signaling in a leptin-responsive cell. A leptin peptide of the present invention binds to but does not activate ObR signaling in a leptin-responsive cell, thereby inhibiting the up-regulatory effects of leptin on ObR signaling in the leptin-responsive cell. Administration of the peptide effectively prevents embryo implantation in a mammal to which the peptide has been administered. Also disclosed herein is a method for identifying a peptide antagonist of ObR, wherein the peptide comprises a leptin sequence.

Abstract: The present invention relates to compositions (i.e., various organic small molecules as exemplified herein) and methods for the inhibition of protein splicing and especially relates to the inhibition of protein autosplicing of intein-containing proteins. Additionally, the present invention relates to the use of the inhibitors of protein splicing of the invention for the treatment of various diseases including but not limited to tuberculosis. Furthermore, the invention provides the first instance of small molecule inhibitors of protein splicing with drug-like characteristics.

Abstract: Disclosed herein are peptides comprising a leptin sequence and methods for their use in preventing ObR signaling in a leptin-responsive cell. A leptin peptide of the present invention binds to but does not activate ObR signaling in a leptin-responsive cell, thereby inhibiting the up-regulatory effects of leptin on ObR signaling in the leptin-responsive cell. Administration of the peptide effectively prevents embryo implantation in a mammal to which the peptide has been administered. Also disclosed herein is a method for identifying a peptide antagonist of ObR, wherein the peptide comprises a leptin sequence.

Abstract: The structures of Edema Factor alone and Edema Factor bound to calmodulin without substrate has been crystallized and its structure determined by x-ray crystallography. Based upon these crystal structures, a method assaying for inhibitors of infection by a bacteria is presented which comprises obtaining a potential inhibitor, obtaining a calmodulin activated adenylyl cyclase exotoxin, obtaining calmodulin, admixing the potential inhibitor, the exotoxin, and the calmodulin, and assaying to determine whether or not the potential inhibitor inhibits production of cAMP by exotoxin.

Abstract: Disclosed are antibodies which catalyze hydrolysis of ?-amyloid. Antibodies generated are characterized by the amide linkage which they hydrolyze. Methods of generating the antibodies by using ?-amyloid peptides which incorporate transition state analogs are also provided. Also disclosed is a vectorized antibody which is characterized by the ability to cross the blood brain barrier, and is further characterized by the ability to catalyze the hydrolysis of ?-amyloid. The vectorized antibody can take the form of bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a taransition state adopted by ?-amyloid hydrolysis.

Abstract: Disclosed herein are peptides comprising a leptin sequence and methods for their use in preventing ObR signaling in a leptin-responsive cell. A leptin peptide of the present invention binds to but does not activate ObR signaling in a leptin-responsive cell, thereby inhibiting the up-regulatory effects of leptin on ObR signaling in the leptin-responsive cell. Administration of the peptide effectively prevents embryo implantation in a mammal to which the peptide has been administered. Also disclosed herein is a method for identifying a peptide antagonist of ObR, wherein the peptide comprises a leptin sequence.

Abstract: Provided herein are methods relating to inhibition of PUMA function for preventing or reducing myocardial cell death. A method for preventing or reducing ischemia/reperfusion induced myocardial cell death in a human is provided as are methods for identifying pharmaceuticals which interfere with PUMA function. Also herein provided is a method for reducing stem cell death in stem cell explants wherein the explants are intended to restore cardiac efficiency following cell death in response to coronary infarct.

Abstract: An antibody and vectorized antibody, capable of crossing the blood brain barrier, which catalyze hydrolysis of ?-amyloid at a predetermined amide linkage are described. The antibody preferentially binds a transition state analog which mimics the transition state adopted by ?-amyloid during hydrolysis. Also described are methods for sequestering free ?-amyloid in an animal's bloodstream or for reducing ?-amyloid or for disaggregating or preventing the formation of amyloid plaques in an animal's brain by administering ?-amyloid specific antibodies or by immunization with endogenous ?-amyloid epitopes.

Abstract: Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a ?-amyloid epitope. Also disclosed are methods for inhibiting the formation of ?-amyloid plaques in the brain of a human, or promoting the disaggregation of a preformed ?-amyloid plaque. Such methods recite the administration of a bispecific antibody.

Abstract: Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a ?-amyloid epitope. Also disclosed are methods for inhibiting the formation of ?-amyloid plaques in the brain of a human, of promoting the disaggregation of a preformed ?-amyloid plaque. Such methods recite the administration of a bispecific antibody.