Abstract: Methods and compositions are provided for the identification of stem cells and cancer stem cells. ?-catenin is also identified as a target for the development of therapeutic moieties against hematopoietic tumors, i.e. leukemia and lymphoma cells, which may include screening assays directed at ?-catenin, or members of the ?-catenin signaling pathway. Cellular proliferation in hematopoietic cells can be altered by introducing stabilized ?-catenin into a hematopoietic cell that is altered in its ability to undergo apoptosis but which is not fully transformed. The immortalized cells are useful in screening assays, and in the analysis of pathways by which hematopoietic cells undergo transformation.

Abstract: A method of assessing the viability of a cell comprises incubating the cell in a culture medium. The culture medium includes a plurality of amino acids and the change in concentration in the medium of at least one amino acid is determined.

Abstract: Human embryonic stem cells form embryoid bodies in culture which contain differentiated human cells. Some of the human cells in embryoid bodies differentiate into cardiomyocytes. Here the biological and electrical characteristics of those cardiomyocytes are described with reference to the use of cardiomyocytes derived from human embryonic stem cells in drug screening protocols for mechanisms of cardiac toxicity.

Abstract: A cloned animal is produced by demecolcine treatment characterized by culturing the nuclear transfer embryo in vitro and transferring the embryo in vivo. This significantly improves in vitro development of somatic cell nuclear transfer embryos and maintenance of pregnancy from transfer of transfer somatic cell nuclear transfer embryos in a surrogate mother up to delivery. A nuclear transfer embryo of a non-primate mammal made by enucleating a recipient oocyte; injecting a nuclear donor cell into the enucleated oocyte; fusing together the injected enucleated oocyte with the injected nuclear donor cell to form a fused oocyte; activating the fused oocyte; and treating the activated oocyte with demecolcine to form the nuclear transfer embryo.

Abstract: Artificial TERT promoters, which are useful for enhancing the differential expression of operably linked heterologous nucleic acid sequences, such as polypeptide cytotoxins, are disclosed herein. Methods for treating disease cells, such as cancer cells, while minimizing effects on normal, somatic cells by administering therapeutically effective amounts of heterologous nucleic acid sequences operably linked to artificial TERT promoters are provided. Kits containing artificial TERT promoters for enhancing differential expression are also provided.

Abstract: A method of enhancing the production of gametes in a transgenic non-human animal is carried out by: (a) providing a transgenic non-human animal comprising cells that contain: (i) a response element; (ii) a nucleic acid encoding FSH? operatively associated with the response element; (iii) an FSH? promoter; (iv) an FSH? locus control region operatively associated with the FSH? promoter; and (v) a nucleic acid encoding a ligand-controllable receptor operatively associated with the FSH? promoter, wherein the receptor binds to the response element in the presence of the ligand when expressed in a host cell; and (b) administering the ligand to the animal in an amount effective to (i) stimulate the production of FSH? in the animal above that found in a corresponding untransformed type animal; and (ii) stimulate the production of gametes in the animal to a level greater than that found in the corresponding untransformed animal.

Abstract: The invention relates to cell preparations comprising cells of the T cell lineage, methods for preparing same, and uses of the cell preparations.

Abstract: The present invention relates, in part, to the C. elegans SKN-1 gene and protein (a transcription factor), and target genes thereof. The invention includes various therapeutic methods and screening methods for identifying antioxidants.

Abstract: The invention provides a method of producing multiple polypeptides, such as antibodies or antibody fragments, in a eukaryotic cell using a single expression vector. The expression vector is engineered to comprise two or more expression cassettes under the control of a single promoter wherein the expression cassettes have splice sites which allow for their alternative splicing and expression as two or more independent gene products at a desired ratio. Use of the vector for the efficient expression of recombinant antibodies in eukaryotic host cells is disclosed as well as the use of such antibodies in diagnostic and therapeutic applications.

Abstract: The present invention claims an invertebrate animal that has been modified to express a set of genes, the set comprising the gene coding for a modified version of the gamma subunit of AMP-activated protein kinase (AMPKg). According to the invention, the animal displays an identifiable phenotype related to lipid metabolism and neurodegeneration. This animal provides a model of neurodegenerative diseases, particularly Alzheimer's disease, and may be useful for screening and testing modulating agents, substances and therapeutic compounds for neurodegenerative disorders.

Abstract: Methods and compositions are provided for modulating cardiac contractility by regulating transcription of the phsopholamban gene using engineered zinc finger proteins.

Abstract: Provided are in vivo screening methods to detect and identify substances that affect neuronal viability, and/or prevent neurodegeneration, and/or confer neuroprotective effects The screening methods utilize recombinant C. elegans expressing a detectable marker in neuronal sub-groups and the use of neurotoxins specific to specific neuronal cells. Also provided are methods for identifying modulators of neurotransmitter transporters such as the dopamine transporter. Therefore, the invention provides methods for identifying substances that can be used in the prevention and therapy of neurodegenerative diseases.

Abstract: A method is described for the production of an animal (offspring) by the process of nuclear transfer. The animal may be produced using donor genetic material in cells taken directly from any stage of an animal, such as an embryo, foetus or adult or from cell cultures established from material from any stage of an animal, such as embryonic, foetal or adult material. The process may be used to introduce genetic modifications into the resultant offspring by genetic manipulation and selection of the cells to act as nuclear donors prior to embryo reconstruction. The present invention provides a method of reconstituting an animal embryo, the process comprising transferring a nucleus into a first oocyte followed by removing and transferring the nucleus from the oocyte to a further oocyte or to an enucleated fertilized zygote.

Abstract: Administration of modified transposon-based vectors has been used to achieve stable incorporation of exogenous genes into animals. These transgenic animals produce transgenic progeny. Further, these transgenic animals produce large quantities of desired molecules encoded by the transgene. Transgenic egg-laying animals produce large quantities of desired molecules encoded by the transgene and deposit these molecules in the egg.

Abstract: The present invention provides transgenic fish whose genome has stably-integrated therein an oncogene operably linked to a promoter. Methods of making the transgenic fish and methods for their use are also provided. In one embodiment, the transgenic fish may advantageously be utilized in methods of screening for drugs or agents that modulate oncogene-mediated neoplastic or hyperplasic transformation, or that modulate sensitivity to chemotherapy or radiation therapy. In another embodiment, the transgenic fish may be used methods of identifying mutations that modulate oncogene-mediated neoplastic or hyperplastic transformation, or that modulate sensitivity to chemotherapy or radiation therapy.

Abstract: A system including: (i) a methodology for targeted cellular ablation in zebrafish; (ii) a methodology for regional cellular ablation in zebrafish. These methodologies are used to identify genetic components that regulate cellular regeneration and to identify drug compounds that influence cellular regeneration for the purpose of developing therapies for degenerative conditions. Transgenic zebrafish disclosed herein contain transgenic constructs composed of: (i) cell and/or tissue-type specific regulatory elements (e.g.

Abstract: A transgenic screen and method for screening biological and chemical test substances or molecules for their ability to influence or modulate the production of BDNF in cells, includes a fusion gene having a zebrafish BDNF gene fragment (promoter) and a fluorescent marker gene inserted downstream of the BDNF gene fragment. When the fusion gene is injected into a zebrafish embryo, the BDNF promoter causes the production of fluorescent protein in various cell types. The embryo is exposed to a test substance for determining the effect thereof on the production of the fluorescent marker protein.

Abstract: The present invention provides methods of screening an agent for activity using teleosts. Methods of screening an agent for angiogenesis activity, toxic activity and an effect cell death activity in teleosts are provided. The invention further provides high throughput methods of screening agents in multi-well plates.

Abstract: Replication-competent adenoviral vectors which selectively replicate in cancer cells are provided. The replication-competent viral vectors comprise an E2F responsive promoter and/or a telomerase promoter operatively linked to an adenoviral coding region. The replication-competent adenoviral vectors effectively replicate in a variety of types of cancer cells and find broad utility in the treatment of cancer.

Abstract: The present invention provides a method of achieving very high targeting efficiency by utilizing targeting vectors that utilize promoter-less selection cassettes and which are engineered to targeted into transcriptionally active loci. In particular, the invention provides a method for targeting promoter-less selection cassettes into transcriptionally active loci in stem cells or other eukaryotic cells with much greater efficiency than previously observed with other methods, thus reducing the number of drug-resistant clones to be screened or eliminating the need to screen for targeted cells altogether. The invention also encompasses the DNA targeting vectors, the targeted cells, as well as non-human organisms, especially mice, created from the targeted cells.