Abstract: The present method is useful for the identification of genes, ORF's and other nucleic acid molecules which are essential for the expression of a specific phenotype in microorganisms. The method employs In vitro transposition in conjunction with an chromosomal integration vector containing a specific gene or genetic element whose function is unknown. Subsequent transformation of a recombination proficient host with the vector and growth first under non-integrating conditions and then under integrating conditions, followed by a selection screen for either single or double crossover events results in transformants that may be subjected to phenotypic screens to determine gene function.

Abstract: The present invention relates to pharmaceutical compositions, kits, and methods of use thereof, comprising, a mutant human herpes simplex-type 1 virus, which is cytopathic to susceptible hyperproliferative cells, such as neoplastic cells. Preferably, the virus does not produce a fully functionally active wild-type ICP0 polypeptide coded for the IE gene 1.

Abstract: A method of liposome-based therapy for a mammalian subject is disclosed. The method uses liposomes with outer surfaces that contain an affinity moiety effective to bind specifically to a biological surface at which the therapy is aimed, and a hydrophilic polymer coating effective to shield the affinity moiety from interaction with the target surface. The hydrophilic polymer coating is made up of polymer chains covalently linked to surface lipid components in the liposomes through releasable linkages. After a desired liposome biodistribution is achieved, a releasing agent is administered to cause cleaving of a substantial portion of the releasable linkages in the liposomes, to expose the affinity agent to the target surface.

Abstract: Nucleotide acid sequences and corresponding translated products of novel mutant forms of the Drosophila DIAP1 gene are described. Such sequences and products are useful in screening methods for identifying and testing agonists and antagonists of DIAP1.

Abstract: A method for identifying a mutation-sensitive active region of a test protein, by providing a test nucleic acid construct comprising a regulatable promoter polynucleotide and a fusion polynucleotide comprising a test polynucleotide encoding the test protein fused to a reporter gene, wherein said fusion polynucleotide is operably associated with the promoter polynucleotide, wherein expression of the fusion polynucleotide in a selected host cell results in a specific phenotype and the presence of the reporter; mutagenizing the test nucleic acid construct to provide a mutagenized construct; transforming a selected host cell with the mutagenized construct to provide a transformed host cell; selecting a transformed host cell that exhibits the reporter, but which does not exhibit the specific phenotype; and sequencing a portion of the mutagenized construct from the selected transformed host cell to determine the alteration of the polynucleotide(s).

Abstract: The present invention provides a method for inhibiting activity of TGF-&bgr;, comprising contacting tissue expressing TGF-&bgr; with an amount of ebaf or an ebaf analogue. The present invention further provides a method for treating a condition associated with overactivity of TGF-&bgr;, particularly fibrosis, a defect in cell proliferation, or a coagulation defect. The present invention also provides a method for inhibiting activity of TGF-&bgr;, comprising contacting tissue expressing TGF-&bgr; with a modulator of ebaf expression, or a modulator of expression of an ebaf analogue. The present invention is further directed to a method for treating fibrosis in a subject in need of treatment, comprising administering to the subject an amount of ebaf or an ebaf analogue effective to treat the fibrosis.

Abstract: Methods and materials are provided for stably introducing any gene into a specific locus in the genome of a microorganism such as yeast without the addition of any drug resistance genes. Specifically provided herein are new genetically engineered inositol-overproducing Saccharomyces cerevisiae strains obtained by using a novel set of yeast integration plasmids that allow the safe, stable, and controlled introduction of homologous as well as heterologous genes into the host genome. In particular, specific loci of the S. cerevisiae yeast genome can be targeted with single or multiple copies of a specific gene that is desired to be expressed or a given set of specific genes that the host can use without the addition of any drug resistance genes. The principles of this new methodology can also be used for the construction of other recombinant yeast and bacterial strains as well as higher eukaryotic cells.

Abstract: This invention provides methods for producing and selecting host cells that better survive transformation treatment by subjecting host cells to conditions that alter them, subjecting the altered cells to transformation conditions, and selecting host cells that survive the transformation conditions. This invention also provides methods for transferring nucleic acids of interest into host cells, using cells that are better able to survive transformation treatment. Also, this invention provides kits for producing or selecting host cells in transformation treatments, as well as, kits comprising various host cells that may be utilized in transformation experiments.

Abstract: The present invention relates to the discovery of a novel Hantavirus. In particular, the present invention relates to nucleic acids of the newly discovered virus and to nucleic acid reagents and antibodies for use in methods of detection and prevention of infection by the virus.

Abstract: The present invention relates to a method for the transformation of a plant characterized by ligating an operon to a vector, the operon containing a promoter and 2-100 genes of interest, and integrating the resulting recombinant vector into a plastid chromosome, to a transformed plant obtained by the method, and the a process for preparing a polyester characterized by culturing or cultivating the transformed plant and collecting the polyester from the cultured or cultivated plant.

Abstract: The present invention relates to a pharmaceutical composition comprising Factor VIII and the divalent metal ions Zn2+ and Cu2+, optionally in the presence of Ca2+ ions and/or Mn2+ ions, wherein said Factor VIII is stable without the addition of albumin. The invention also relates to a method for the production of recombinant Factor VIII from mammalian cells carrying the gene therefor, comprising culturing said mammalian cells in medium free of plasma-derived protein and supplemented with divalent metal ions, including Cu2+ and Zn2+, and optionally in the presence of Ca2+ and Mn2+ ions.

Abstract: The present invention relates to novel yeast cells with increased permeability to compounds, such as small organic compounds. In particular, the invention provides genetically modified yeast cells carrying functional, preferably conditionally regulated, copies of HXT9 and HXT11 genes integrated in the chromosome at the PDR1 and PDR3 loci, thereby disrupting the PDR1 and PDR3 gene activity. The invention further relates to methods and compositions for the use of these hyperpermeable yeast cells for screening for compounds that modulate macromolecular interactions. The invention is exemplified by the use of the hyperpermeable yeast cells in such a screening system. In addition, the invention further provides methods of producing the yeast cells of the invention, as well as polynucleotides, vectors, and kits for use of the hyperpermeable yeast cells and the screening methods of the invention.

Abstract: The present invention is directed to isolated transducing phages, methods of isolating transducing phages, and methods of using transducing phages including, for instance, transferring at least one nucleic acid fragment from a donor microbe to a recipient microbe, and producing a secondary metabolite from a microbe. The transducing phages typically have a broad host range, and transduce microbes in the Order Actinomycetales, in particular in the Family Streptomycetaceae, including Streptomyces coelicolor, Streptomyces lividans, Streptomyces venezuelae, Streptomyces avermitilis, and Saccharopolyspora erythraea. The transducing phages can be specialized transducing phages or generalized transducing phages.

Abstract: The present invention relates to host cells suitable for expressing genes under the direction of foreign RNA polymerases and to providing very low levels of expression of such genes and RNA polymerases in the absence of induction.

Abstract: The invention features a method of modulating, e.g., inhibiting or promoting, the spatial or positional relationship of a cell to a substrate, or modulating the intracellular response of a cell to a substrate, in vitro or in vivo. The method includes administering an agent which modulates the interaction, e.g., the binding, of the syndecan-4 ectodomain with a counterligand, thereby modulating the spatial or positional relationship of a cell to a substrate, or modulating the intracellular response of a cell to a substrate. The preferred counterligand is an ECM component, e.g., the heparin-binding domain of a component of the extracellular matrix (ECM) such as fibronectin, vitronectin, a laminin or a collagen. The invention also features methods of identifying compounds which modulate, e.g.

Abstract: A method for identifying a nucleic acid which codes for a polypeptide factor affecting the covalent bonding of polypeptides to the surface of Gram-positive bacteria, comprising the following steps: a) providing a sample of Gram-positive bacteria which can be genetically altered and contain or produce at least one enzymatic reporter substance which is or can become covalently bonded to the surface of the Gram-positive bacteria, said at least one reporter substance having a different enzymatic activity when not covalently bonded to the surface of the Gram-positive bacteria from that exhibited when it is covalently bonded to the surface of the Gram-positive bacteria; b) causing genetic alterations in Gram-positive bacteria of the sample; c) assaying the enzymatic activity of the reporter substance of the Gram-positive bacteria of the sample; d) separating Gram-positive bacteria which exhibit a different enzymatic activity of the reporter substance from that observed for covalent bonding of the reporter subst

Abstract: The present invention relates to novel bacterial strains useful for the production of 2-keto-L-gulonic acid. The present invention further relates to the use of these strains for the production of 2-keto-L-gulonic acid by fermentative conversion of L-sorbose. The present invention further relates to the use of these novel bacterial strains for the production of pyrroloquinoline quinone and a nontoxic lipopolysaccharide. Also described is the strains of the present invention transformed by a vector.

Abstract: The invention provides a novel gene, gridlock, and its encoded protein. gridlock plays a role in vascular development and modeling, and a mutation in gridlock has been associated with an aortic arch disease, coarctation. Thus, gridlock nucleic acid molecules and polypeptides can be used in methods of diagnosing, treating, and preventing gridlock-related diseases and conditions, such as aortic arch diseases.

Abstract: The invention concerns human cells which, due to an activation of the endogenous human EPO gene, are able to produce EPO in an adequate quantity and purity to enable a cost-effective production of human EPO as a pharmaceutical preparation. Furthermore the invention concerns a process for the production of such human EPO-producing cells, DNA constructs for the activation of the endogenous EPO gene in human cells as well as a process for the large-scale production of EPO in human cells.

Abstract: Methods for extracting DNA from a biological sample that result in a higher yield of target DNA than conventional methods. More particularly, methods for extracting DNA include exposing the biological sample to inhibitors of DNA degradation.