Abstract: The present invention provides methods for detecting epigenetic, multigenerational DNA alterations caused by toxicants such as endocrine disruptor agents in a subject. The practice of the present invention can be used to diagnose and/or treat a subject having the identified DNA alterations by developing therapeutics, to prevent or delay the onset of associated diseases and/or dysfunctions.

Abstract: The present invention is directed to long-lasting therapeutic formulations and their methods of use wherein the formulation comprises a genetically modified micro-organ that comprises a vector which comprises a nucleic acid sequence operably linked to one or more regulatory sequences, wherein the nucleic acid sequence encodes a therapeutic polypeptide, such as erythropoietin or interferon alpha.

Abstract: Disclosed herein are methods for producing liver precursor cells as well as hepatocyte cells form pluripotent and/or multipotent cells. Also disclosed herein are methods of enriching isolating and/or purifying liver precursor cells and/or hepatocyte cells. Further disclosed are compositions comprising cell cultures and cell populations that are enriched for liver precursor cells or hepatocyte cells.

Abstract: The present invention provides a method for producing mesenchymal cells for production of mesenchymal cells for formation of a tooth, the method comprising: culturing totipotent stem cells in the presence of a differentiation inducer to produce a cell population after differentiation induction treatment, the cell population containing CD44-positive and CD29-positive cells or CD44-positive and CD106-positive cells; and selecting, from the cell population after the differentiation induction treatment, the CD44-positive and CD29-positive cells or CD44-positive and CD106-positive cells as the mesenchymal cells for the formation of the tooth.

Abstract: A biologic intervention method and apparatus generates a persistent modification to an AV node that is physiologically stable after the agent has matured but is alterable with subsequent application of an agent. Specifically, the generic agent is used to modulate a node in a cardiac conduction system including rate control using one and a combination of a family of K+ channel or equivalent. Specifically, the channel is implemented to slow conduction by generating an outward current during optimization of action potential and repolarization phase thus decreasing the current that is available to excite downstream cells. A Kv 1.3 channel, for example, may be used as the biologic channel. The invention enables reversal of the modulation or adjustment for various heart rates (BPM) based on medical and patient-specific needs.

Abstract: The present invention provides novel methods of maintaining genetic stability of non-human animal inbred strains. In the methods, pedigree-tracked cryopreserved embryos or gametes or pre-gametes derived from a foundation colony are produced and used to re-establish the foundation colony at appropriate intervals.

Abstract: Methods and compositions for the rapid and reversible destabilizing of specific proteins in vivo using cell-permeable, synthetic molecules are described.

Abstract: The present invention is directed to long-lasting erythropoietin therapeutic formulations and their methods of use wherein the formulation comprises a genetically modified micro-organ that comprises a vector which comprises a nucleic acid sequence operably linked to one or more regulatory sequences, wherein the nucleic acid sequence encodes erythropoietin.

Abstract: Methods for differentiating human pluripotent stem cells into islet-like cells are provided. In certain embodiments, the methods utilize sequential culturing of the human pluripotent stem cells with certain factors to produce islet-like cells. In certain embodiments, the population of cells produced by the methods is further enriched for islet-like cells.

Abstract: The present invention provides novel methods for treating diseases associated with apoptotic degeneration in ocular tissue cells by effective administration of pigment epithelium derived factor (PEDF). The present inventors studied PEDF as a means to prevent ganglion cell death, the final pathology of glaucoma. The present invention is particularly focused on SIV vectors for effective methods for delivering PEDF, and constructed an SIV-PEDF vector. When the SIV-PEDF vector was administered subretinally to an ischemia reperfusion model and NMDA-induced model, a significant suppression effect on ganglion cell death was observed. The present inventors therefore discovered that the SIV-PEDF vector is an effective pharmaceutical agent for treating diseases associated with apoptotic degeneration in ocular tissue cells, such as glaucoma.

Abstract: The present invention relates to a modified and optimized Factor VIII or Factor IX nucleic acid for inclusion in a chimeric virus vector. Use of such vector can be used for treatment of hemophilia.

Abstract: The present invention provides novel methods of maintaining genetic stability of non-human animal inbred strains. In the methods, pedigree-tracked cryopreserved embryos derived from a foundation colony are produced and used to re-establish the foundation colony at appropriate intervals.

Abstract: A method for forming an organ and/or tissue from undifferentiated cells derived from a vertebrate animal in vitro, which comprises the step of culturing the undifferentiated cells derived from a vertebrate animal in the presence of a retinoic acid X receptor ligand (e.g., a retinoic acid X receptor agonist or antagonist), and a method for forming a pancreas from undifferentiated cells derived from a vertebrate animal in vitro or a method for forming a tissue having morphology and function of a pancreas from undifferentiated cells derived from a vertebrate in vitro, which comprises the step of culturing the undifferentiated cells derived from a vertebrate animal in the presence of a retinoic acid receptor ligand, together with activin, that does not substantially bind to the retinoic acid receptor subtype ?.

Abstract: The invention relates to the generation of non-human transgenic animals comprising a reporter construct for producing a detectable amount of a reporter molecule operably linked to a transcriptional regulatory nucleic acid molecule from the human CYP3A4 gene located between the initiation of transcription site of the gene and a position located 13,000 nucleotides upstream from the site. The invention also relates to the use of these animals for determining the effect of a compound, particularly, but not exclusively, a xenobiotic or steroid, on the regulation of expression of the CYP3A4 gene in a human.

Abstract: The present invention encompasses methods and apparatus for minimizing the risks inherent in endovascular grafting for blood vessel therapy and repair. The invention involves delivering adult stem cells, embryonic stem cells, progenitor cells, fibroblasts, or smooth muscle cells to the diseased blood vessel, in some embodiments in conjunction with a stent graft.

Abstract: The present invention relates to a method for recombinant manufacturing of substances, wherein cells are transformed suing a nucleotide sequence coding for the substance, the transformed cells are subjected to a cloning process, and the cells obtained in this fashion are introduced into a host organism. The present invention relates in particular to the use of the method in the production of recombinant proteins, cells and tissues. According to a further aspect, the invention relates to a method, wherein the cells of an individual are isolated, said sells are introduced into an immunoincompetent animal for further growth and the cells, tissue and/or organs cultivated in the animal are again isolated and introduced into an individual.

Abstract: The present invention relates to an antitumor immune response, and in more detail, to a method for inducing cytotoxic T lymphocytes specific to a tumor-associated antigen that acts specifically on tumor cells. Immunotherapy using the present invention may be most effective among immune therapies that use immunity of our body, because in the present invention, CEA-specific cytotoxic T lymphocytes can be induced in vitro by using a dendritic cell transduced with a recombinant adenovirus. Further, immunotherapy using the present invention can function as a powerful tool for tumor prevention or treatment, if being used in combination with antitumor vaccines or other treatments.

Abstract: Disclosed are methods and systems for preventing or treating cardiac dysfunction, particularly cardiac pacing dysfunction by genetic modification of the conduction system of the heart. In one embodiment, the invention provides a method of genetically modifying the cells by delivering to the cells one or more coding sequence in a genetic construct capable of modifying the expression of ion channels of the cells.

Abstract: Disclosed is an invention for focally modulating the activity of a calcium channel in a mammal. In one aspect, the invention features a method that includes contacting a pre-determined tissue or organ region with a nucleic acid sequence encoding a GEM protein or a variant thereof to express the GEM protein or variant within the region. Typical methods further include expressing the GEM protein or variant so as to modulate the activity of the calcium channel. The invention has a wide spectrum of useful applications including treating a medical condition associated with unsuitable calcium channel activity.

Abstract: A method and composition for improving one or more indicators of bowel health or metabolic health in a mammalian animal. This comprises the delivering to the gastrointestinal tract of the animal an effective amount of an altered wheat starch in the form of or derived from the grain of a wheat plant. The proportion of amylose in the starch of the grain is at least 30%.