Abstract: The present invention relates to methods for increasing the efficiency of transformation of cycling cells, the methods comprising synchronizing cells at a first stage of the cell cycle, and transforming the cells at a second stage of the cell cycle within about one cell cycle of the first stage with a genetically engineered nucleic acid that encodes a desired gene product. The invention further relates to cancer therapy and, in particular, to methods of efficiently transforming cancer cells with nucleic acids that encode gene products that inhibit the growth of cancer cells.

Abstract: Presenilin Associated Membrane Protein (PAMP), and nucleic acids encoding this protein, are provided. PAMP and PAMP nucleic acids provide diagnostic and therapeutic tools for evaluating and treating or preventing neurodegenerative diseases. In a specific embodiment, mutations in PAMP are diagnostic for Alzheimer's Disease or spina bifida. The invention further relates to screening, particularly using high-throughput screens and transgenic animal models, for compounds that modulate the activity of PAMP and presenilins. Such compounds, or gene therapy with PAMP, can be used in treating neurodegenerative diseases, particularly Alzheimer's Disease. In addition, the invention provides PAMP mutants, nucleic acids encoding for PAMP mutants, and transgenic animals expressing PAMP mutants, which in a preferred aspect result in biochemical changes similar to those induced by mutations in &bgr;APP, PS1, or PS2, associated with familial Alzheimer's disease.

Abstract: The TGF-&bgr; family of growth factors, particularly the bone morphogenetic protein (BMP)-2/4 homolog decapentaplegic (dpp), are specifically required to maintain germline stem cells and promote their division. Overexpression of dpp blocks germline stem cell differentiation. Mutations in dpp or its receptor saxophone accelerate stem cell loss and retard stem cell division. dpp signaling is directly received by germline stem cells, and thus dpp signaling helps define a niche that controls germline stem cell proliferation.

Abstract: A plant-based edible vaccine against autoimmune disease prepared by expressing a CTB-autoantigen chimeric gene construct in plant cells and transgenic plants is disclosed. DNA constructs, expression vectors comprising a nucleotide sequence that encodes a CTB-autoantigen chimeric gene, which are optimized for expression in plants, are described.

Abstract: Disclosed are methods and pharmaceutical compositions for inducing pancreatic hormone production.

Abstract: The invention provides methods of introducing heterologous cells into fish. After introduction cells remain viable, and in some instances proliferate, for sufficient time to conduct a variety of analyses on the heterologous cells or the fish or both. Such methods are useful for screening potential drugs for toxicity toward introduced cells or for capacity to stimulate differentiation and/or proliferation of introduced cells. Such methods are also useful for diagnosing the presence of small quantities of cancerous cells or pathogens in patient tissue samples. Such methods are also useful for culturing cells for subsequent use in cell or tissue engineering.

Abstract: (1) Transgenic medaka fish into which a polynucleotide having the nucleotide sequence from 211 to 1935 position represented by Sequence ID No: 1 is introduced, (2) A method of producing medaka fish having one or more thrombi, comprising the step of raising the transgenic medaka fish described in (1) in the presence of estrogen, (3) Medaka fish having one or more thrombi produced by the method described in (2), and (4) A method of testing an estrogen-like acting substance, comprising the steps of raising the transgenic medaka fish described in (1) in test water, and observing whether or not one or more thrombi are formed in the medaka fish after the raising step.

Abstract: A composition for in vitro and in vivo transfection of vertebrate male germ cells comprises a nucleic acid or transgene, and a gene delivery system, and optionally a protective internalizing agent, such as an endosomal lytic agent, a virus or a viral component, which is internalized by cells along with the transgene and which enhances gene transfer through the cytoplasm to the nucleus of the male germ cell. A method of genetically altering a vertebrate male germ cell in vivo employs a lentiviral-derived vector. A method of substantially depopulating a vertebrate testis employs a combination of a dose of an alkylating agent, such as busulfan, chlorambucil, cyclophosphamide, melphalan, or ethyl ethanesulfonic acid, and a dose of gamma radiation. A pharmaceutical preparation and a transfer kit utilize the composition. A method for introducing a polynucleotide into vertebrate male germ cells comprises the administration of the composition to a vertebrate.

Abstract: An improved prosthetic graft for the bypass, replacement or repair of vessels and organs that are in contact with blood flow is disclosed. The prosthetic graft includes a porous prosthetic implant and adherent cells adhered to the outer surface of the implant. The adherent cells are transfected with at least one recombinant nucleic acid molecule encoding at least one protein that enhances patency of the graft. The prosthetic graft has a long-term patency and success rate that is superior to other previously described prosthetic grafts designed for such use. Also disclosed are methods of making and using such a graft.

Abstract: This invention responds to a long felt need, by providing in one embodiment, a helper virus based on the Ad2 serotype for use in the Cre/loxP system for the generation of Ad vectors deleted of all Ad protein coding sequences. Using this and helper virus based on Ad5, genetically identical hdAd that differ only in the virion protein components, which are derived from the helper virus, were produced. The vectors have identical expression characteristics in vitro, regardless of the serotype, and the sequential use of hdAd of different serotypes allows for successful repeat vector administration in vivo.

Abstract: Disclosed are a DNA which encodes murine trehalase, a polypeptide expressed by the DNA, and a transgenic- and knockout- animals which have been genetically engineered with the DNA. The DNA comprises a part or the whole of the nucleotide sequence of SEQ ID NO:1.

Abstract: The invention provides methods for generating, identifying, and selecting polynucleotides encoding novel starch metabolizing enzymes (NSME), NSME-encoding polynucleotides, compositions of recombinant shuffled NSME protein, plant cells and microbes containing a shuffled NSME polynucleotide in expressible form, plants containing a shuffled NSME polynucleotide in expressible form, novel starch compositions produced by plants and cells, uses of such plants, cells, and starch compositions.

Abstract: Recombinant adenoviruses comprising a heterologous DNA sequence coding for basic blast growth factors (bFGF), preparation and uses thereof for the treatment and/or prevention of neurodegenerative diseases.

Abstract: Human mesenchymal stromal cells can be induced to differentiate into oligodendrocytes and neurons, respectively. For these cell types, therefore, MSCs can be a therapeutic source, either in vitro or in vivo, in the context of treating pathologies of the central nervous system which are characterized by neuron loss, such as Parkinson's disease, Alzheimer's disease and stroke, as well as head trauma, or by dysfunction in ganglioside storage or demyelinization, such as Tay-Sachs disease, G1 gangliosidosis, metachromatic leukodystrophy, and multiple sclerosis.

Abstract: The present invention provides a safe immortalized bone marrow mesenchymal stem cell obtained by transferring a cell proliferation factor gene inserted between a pair of site-specific recombination sequences to a bone marrow mesenchymal stem cell.

Abstract: The invention provides a microinsertion-based, trans-complementation method of in vitro oocyte activation useful to identify properties of sperm-borne oocyte-activating factor(s) (SOAF) and ooplasmic interactions with sperm components at fertilization. The invention provides at least one detergent-insoluble heat-sensitive component of the perinuclear matrix of a spermatozoon (SOAFm) that acts coordinately with at least one heat-stable submembrane sperm component. SOAFm is solubilized in vitro (SOAFs) under reducing conditions similar to those encountered in the ooplasm. By the method of the invention, the failure of heat-inactivated demembranated sperm heads to activate an egg is rescued by coinsertion of SOAFs into an oocyte. SOAFs is protease-sensitive and is liberated from demembranated heads in a temperature-dependent manner that inversely correlates with the ability of demembranated sperm heads to activate oocytes.

Abstract: Cell-based gene transfer is effected by administering transfected cells containing an expressible transgene into the pulmonary system of a patient, where the cells express and secrete expression products of the transgene directly into the pulmonary system. Also provided is the use of angiogenic factors in treatment of pulmonary hypertension.

Abstract: The invention features a method of promoting an alteration at a selected site in a target DNA, e.g., in the chromosomal DNA of a cell. The method includes providing, at the site: (a) a double stranded DNA sequence which includes a selected DNA sequence; (b) an agent which enhances homologous recombination, e.g., a Rad52 protein or a functional fragment thereof; and (c) an agent which inhibits non-homologous end joining, e.g., an agent which inactivates Ku such as an anti-Ku antibody or a Ku-binding oligomer or polymer, and allowing the alteration to occur. The agent which inhibits non-homologous end joining, e.g., a Ku inactivating agent such as an anti-Ku antibody, is preferably provided locally. Components (a), (b), and (c) can be introduced together, which is preferred, or separately.

Abstract: The invention relates to methods for treatment of neurological disease by administering an agent which interacts with a retinoid receptor associated with the neurological disease. The invention is also related to a method of modulating dopamine receptor synthesis by introducing an agent that interacts with a retinoid receptor associated with the dopamine receptor synthesis. The invention is further related to a transgenic animal, e.g., mouse, and mammalian cell line, which is deficient in the normal synthesis of one or more receptors of RAR&agr;, &bgr;, &ggr; and RXR, and cell line thereof.

Abstract: The invention is directed to a method of in vivo selection for genetically modified hematopoietic progenitor cells from nonmodified hematopoietic cells in a subject. Ibis goal is accomplished by introducing mutant dihydrofolate reductase genes into hematopoietic progenitor cells and then administering to a subject harboring the resultant transformed cells an antifolate and a nucleoside transport inhibitor. The invention is also directed to nucleic acids encoding mutant dihydrofolate reductase genes and to hematopoietic cells transformed with such mutant genes.