Abstract: This disclosure shows that the BPV-1 E2 protein-dependent minichromosome maintenance element (MME) comprised of E2 multimeric binding sites can provide the stable maintenance replication function to the mouse polyomavirus (PyV) core origin plasmids in the presence of BPV-1 E2 protein and PyV large T-antigen (LT). MME dependent plasmids are lost with the frequency of 6% per generation. Significantly long stable maintenance replication can also be provided without selection pressure. We also demonstrate that PyV core origin maintenance function/replication activation could be provided by Epstein-Barr virus Family of repeats and EBNA1 protein. The maintenance of the Polyomavirus core origin plasmid was characterized by 13% loss of the plasmid during one cell generation in the case of EBV FR harboring plasmids.

Abstract: The invention features ABC1 nucleic acids and polypeptides for the diagnosis and treatment of abnormal cholesterol regulation. The invention also features methods for identifying compounds for modulating cholesterol levels in an animal (e.g., a human).

Abstract: The present invention is directed to novel recombinant nucleic acids for introducing yeast chromosomal elements into the genomes of bacteria. The invention provides methods to convert the modified bacterial genomes into artificial yeast chromosomes by fusing the bacteria with yeast that linearize the modified bacterial genomes, to produce artificial chromosomes.

Abstract: Agents and methods to alter rAAV transduction are provided.

Abstract: A nephropathy-associated gene which encodes a transcription repressor; and a nonhuman transgenic animal suffering from nephropathy which is constructed by transferring the above gene and allows the observation of increases in urinary volume, urinary albumin and urinary NAG, pyelectasis, enlargement in kidney tubule and glomerular swelling at the early stage and the following sclerosis.

Abstract: The invention features a method of identifying a compound that inhibits (a) the physical interaction (binding) between MUC1 and tumor progressors (e.g., ?-catenin, c-Src, EGF-R, p120ctn, or PKC?) and/or (b) phosphorylation of MUC1 by tumor progressors with kinase activity (e.g., c-Src, EGF-R, or PKC?). The invention also includes a method of inhibiting an interaction between MUC1 and ?-catenin and a method of inhibiting expression of MUC1 or a tumor progressor in a cell.

Abstract: The present invention provides recombinant viruses which replicate the viral genome selectively in response to the intracellular conditions of the target cell through the use a pathway-responsive promoter which substantially inhibits viral replication in the host cell based on the phenotypic or genotypic of the infected cell. In the target cell, the promoter element of the pathway-responsive promoter is inactive and thus the virus is permitted to replicate. This results in: (1) killing the cells by natural lytic nature of the virus, and/or (2) provides a therapeutic dose of a transgene product (amplified in comparison to replication incompetent vectors) to the target cell, and (3) producing a localized concentration of the virus facilitating the infection of surrounding cells to the recombinant virus.

Abstract: This invention relates to pharmaceutical compositions comprising plant deoxyribonucleoside kinase enzymes (dNK) capable of phosphorylating nucleoside analogs and to medical use of said dNKs. More specifically the invention relates to the medical use of deoxyribonucleoside kinase enzymes derived from (Arabidopsis thaliana), from loblolly pine (Pinus taeda), from tomato (Lycopersicum esculentum), from maize (Zea mays) or from rice (Oryza sativa). The invention also relates to methods of sensitizing cells to prodrugs, and to methods of inhibiting pathogenic agents in warm-blooded animals using said plant dNKs. In another aspect the invention relates to plant derived deoxyribonucleoside kinase enzymes provided in isolated form from loblolly pine (Pinus taeda), from tomato (Lycopersicum esculentum), from maize (Zea mays) or from rice (Oryza sativa).

Abstract: The invention relates to a method for obtaining a chromosomal locus for transgenesis of a multicellular eukaryotic organism, “MEO”, to a vector for transgenesis by homologous recombination of a MEO and to the use of such an vector for trans-genesis by homologous recombination of a MEO and to the transgenic MEO thus obtainable.

Abstract: In a first aspect the present invention provides a tumor cell line stably transfected with an expression vector containing a reporter gene, preferably a fluorescent protein, operably linked to a promotor that also controls expression of a protein that is associated with tumor regression, stabilization of tumor growth or inhibition of metastatic growth, characterized in that said cell line is capable to form a tumor when implanted or injected into the non-human animal. Compared to the traditional in vivo models, the present invention differs in that the reporter gene is not constitutively expressed, but only after exposure to a test compound that results in the expression of a protein or enzyme associated with tumor regression, stabilization of tumor growth or inhibition of metastatic growth.

Abstract: The present invention relates to an isolated Period 1 (Per1) promoter DNA inducing rhythmical expression of a gene operably linked thereto. This invention also provides a DNA comprising a Period 1 promoter DNA and a gene operably linked thereto, the gene being under the regulation of the promoter DNA. The present invention further provides transformants and transgenic mammals into which the DNA has been introduced. The transformants and transgenic mammals are useful in the screening of pharmaceutical drugs against diseases and disorders pertaining to the circadian rhythm.

Abstract: The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers and an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers and an immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunomers according to the invention further comprise at least two oligonucleotides linked at their 3? ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunomodulatory oligonucleotide and having an accessible 5? end.

Abstract: The present invention provides derivatives of ethanologenic Escherichia coli K011 constructed for the production of lactic acid. The transformed E. coli of the invention are prepared by deleting the genes that encode competing pathways followed by a growth-based selection for mutants with improved performance. These transformed E. coli are useful for providing an increased supply of lactic acid for use in food and industrial applications.

Abstract: This invention demonstrates that KRC molecules have multiple important functions as modulating agents in regulating a wide variety of cellular processes including: inhibiting NFkB transactivation, increasing TNF-alpha induced apoptosis, inhibiting JNK activation, inhibiting endogenous TNF-alpha expression, promoting immune cell proliferation and immune cell activation (e.g., in Th1 cells), activating IL-2 expression e.g., by activating the AP-1 transcription factor, and increasing actin polymerization. The present invention also demonstrates that KRC interacts with TRAF. Furthermore, the present invention demonstrates that KRC physically interacts with the c-Jun component of AP-1 to control its degradation Methods for identifying modulators of KRC activity are provided. Methods for modulating an immune response using agents that modulate KRC activity are also provided.

Abstract: The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers and an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers and an immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunomers according to the invention further comprise at least two oligonucleotides linked at their 3? ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunomodulatory oligonucleotide and having an accessible 5? end.

Abstract: The present invention is based on the discovery that teeth primordia can be generated using bone marrow cells and that bone marrow cells may be employed to generate teeth without the need for purification and expansion of a population of cells.

Abstract: The invention provides an immunostimulatory nucleic acid. In certain embodiments according to this aspect of the invention, the sequence of the immunostimulatory oligonucleotide and/or immunomer is at least partially self-complementary.

Abstract: The present invention provides immortalized eukaryotic cells and methods useful for the production of immunologically active bivalent antibody fragments, such as F(ab?)2 fragments. The methods and cells of the invention result in a desirable ratio of bivalent to monovalent antibody fragments.

Abstract: Novel double and triple fusion reporter gene constructs harboring distinct imageable reporter genes are provided, as well as applications for the use of such double and triple fusion constructs in living cells and in living animals using distinct imaging technologies.

Abstract: A vector and a method are provided for delivering a nucleic acid to a nervous system cell. The vector includes a first nucleic acid, a second nucleic acid, inverted terminal repeats of adeno-associated virus, and a tetracycline-off regulatable promoter system that includes a first promoter operably linked to the first nucleic acid and a second promoter operably linked to the second nucleic acid. The promoters drive expression in opposite directions and away from the inverted terminal repeats. The method includes providing a recombinant adeno-associated viral (rAAV) vector and administering the vector to a nervous system cell. Expression of a product from the first nucleic acid is regulatable by the promoter system.