Abstract: Acidic amino acid extensions to multimeric nucleic acid (e.g., DNA or RNA) binding proteins provide novel nucleic acid binding proteins which can inhibit the function of cellular proteins, thereby regulating and controlling cell growth. The nucleic acid binding proteins are engineered to contain a plurality of acidic amino acids appended to the proteins, generally as extensions of the multimerization or dimerization domain at the amino terminus. The acidically extended nucleic acid binding proteins act as potent dominant negatives which were demonstrated to inhibit the activation of endogenous transactivators, such as AP1. The invention provides novel methods to create DNA binding proteins which can specifically and stably heterodimerize with cellular regulatory proteins and control cell growth. Suitable nucleic acid binding proteins for acidic extensions include members of transcription regulatory protein families, e.g.

Abstract: The present invention provides a plasmid containing a promoter sequence, a nucleotide sequence encoding an exogenous protein, and a nucleotide sequence encoding an enzyme capable of modifying the exogenous protein. In a specific embodiment of the invention the encoded exogenous protein is human .beta.-casein and the encoded enzyme is a human kinase capable of phosphorylating recombinant .beta.-casein in a bacterial system. Phosphorylated recombinant human .beta.-casein synthesized using the plasmid of the invention is shown to have the same bioactivity as native human .beta.-casein.

Abstract: A method of inhibiting the growth of bFGF-dependent neoplastic cells is disclosed. The method includes the steps of accessing a selected colony of such cells and adding a bFGF-specific antisense primer to such colony. By performing the adding step, there is downregulating of the expression of colony-intracellular bound bFGF, and by performing the downregulating step, there is inhibiting of bFGF-promoted growth of cells in the colony.

Abstract: The present invention relates, in general, to novel TPR-containing genes, tpr1 and tpr2. In particular, the present invention relates to nucleic acid molecules coding for tpr1 and tpr2; purified tpr1 and tpr2 polypeptides; recombinant nucleic acid molecules; cells containing the recombinant nucleic acid molecules; antibodies having binding affinity specifically to tpr1 and tpr2 polypeptides; hybridomas containing the antibodies; nucleic acid probes for the detection of tpr1 and tpr2; a method of detecting the novel tpr1 and tpr2 nucleic acids or polypeptides in a sample; and kits containing nucleic acid probes or antibodies. Therapeutic uses for the tpr1 and tpr2 polypeptides are also provided.

Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of weight, and to the diagnostic and therapeutic uses to which such modulators may be put. In its broadest aspect, the present invention relates to the elucidation and discovery of nucleotide sequences, and proteins putatively expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight. The nucleotide sequences in object represent the genes corresponding to the murine and human ob gene, that have been postulated to play a critical role in the regulation of body weight and adiposity. Preliminary data, presented herein, suggests that the polypeptide product of the gene in question functions as a hormone.

Abstract: A method for identifying regulators of integrin activation by establishing a selected cell line which contains a functional integrin and a chimeric polypeptide having a cytoplasmic domain of an integrin subunit fused to a polypeptide containing extracellular and transmembrane domains that are not functional integrin domains, so that chimera can inhibit signaling activities of the functional integrin by interaction with integrin regulator molecules in the cytoplasm; transfecting the cell line with a selected cDNA expression library; expressing proteins of the cDNA expression library; and identifying proteins which when overexpressed overcome the inhibition of signaling activities by said chimeric polypeptide, said proteins being regulators of integrin. Methods of designing drugs to modify integrin function and cell lines for screening regulators of integrin activation are also provided.

Abstract: The invention relates to a vector for transforming microorganisms capable of undergoing sporulation and which contains itself a heterologous insert comprising a DNA sequence coding for at least part of crystal protein, particularly that of B. thuringensis. It also concerns the polypeptides expressed by said microorganisms and having insecticidal properties similar to those of crystal protein, the microorganisms themselves, as transformed by this vector and insecticidal composition including either said polypeptide or the microorganism itself.

Abstract: A vector, in particular a retroviral vector, which includes a heterologous or foreign gene and a gene encoding a negative selective marker. The negative selective marker enables one to kill cells which contain the gene encoding the negative selective marker, when a particular agent is administered to such cells.

Abstract: Vectors and recombinant bacteria for overproducing riboflavin, in which nucleic acid overproducing riboflavin biosynthetic proteins is introduced in the chromosome of the host organism, e.g. at multiple sites and in multiple copies per site. A rib operon having at least five genes is used to make such recombinant bacteria.

Abstract: An isolated DNA sequence capable of directing gene expression comprising a hRAR-.alpha. promoter or a hRAR-.alpha. promoter element, expression vectors containing the DNA sequence and host cells containing the expression vectors.

Abstract: Strains of Trichoderma spp. that are improved in their capacity as biological control agents for phytopathogenic fungi and nematodes are obtained that are able to over-produce a proteinase, with the aid of a transformation method which involves introducing the gene prb1 of Trichoderma that codes for the proteinase PrB1 under the control of adequate means of regulating expression, producing multiple copies in a stable manner; this ensures that the control achieved of the disease that is caused by pathogenic fungi or nematodes is better in the transgenic strain than in the uncultivated strain that is used as a receptor of the genetic information.

Abstract: A gene trap construct for identification of genes whose activity is regulated upon a cellular transition event which comprises in downstream sequence (i) a cassette having a functional splice acceptor, a translation stop sequence and an internal ribosome entry site and (ii) a promoterless protein coding sequence encoding at least one polypeptide providing positive and negative selection traits. A method for identification of genes whose activity is regulated upon a cellular transition event by introducing the gene trap construct into a cell and observing expression of the positive and/or negative selection traits before and after the transition event.

Abstract: This invention related to constructs comprising mutant HIV genomes having an alteration in a nucleotide sequence which is critical for genomic RNA packaging and non-infectious, immunogenic HIV particles produced by expression of these constructs in mammalian cells. Cell lines which stably produce non-infectious, immunogenic HIV particles are also included. Prophylactic and therapeutic vaccines, diagnostic reagents, and related methods are further described.

Abstract: Escherichia coli characterized in that a capability thereof of forming acetate is at most one fifth that of wild type Escherichia coli, and a process for producing a useful substance by cultivating the Escherichia coli to a high density and recovering the substance

Abstract: This invention provides a method for obtaining a recombinant retroviral packaging cell capable of producing retroviral vectors and the recombinant packaging cell obtained by the method. Also provided is a method of producing recombinant retroviral particles obtained by introducing into the packaging cells obtained according to the methods disclosed herein, a recombinant retroviral vector and propagating the resulting producer cells under conditions favorable for the production and secretion of retroviral vector supernatant. The retroviral supernatants produced by these methods also is claimed herein. This invention further provides a method for screening retroviral vector supernatant for high transduction efficiency and methods for producing retroviral vector supernatant for transducing cells with high efficiency in gene therapy applications.

Abstract: There are provided a method and a kit for testing microbial drug resistance and a method and a kit for measuring minimum inhibitory concentration for a microorganism, in which highly reliable evaluation results are obtained by preventing false evaluation based on false-resistance of microorganisms to a drug. The method of testing microbial drug sensitivity comprises inoculating and culturing a microorganism in a drug-containing medium to obtain a medium containing the microorganism morphologically transformed by the influence of the drug, adding an ATP elution agent and an ATP deletion agent to the culture to delete the eluted ATP and other ATP in the medium, and comparing the amount of ATP in the microorganism remaining in the culture with the amount of ATP in the microorganism separately cultured in a medium not containing said drug and treated in the same manner as above. The method of measuring minimum inhibitory concentration for a microorganism is carried out in the same manner as above.

Abstract: The present invention exploits the discovery that certain single base changes in the gacA gene coding sequence, which result in certain single amino acid changes in the encoded GacA protein, render it LemA-independent. The present invention therefore provides DNA that encodes mutant GacA proteins that do not require phosphorylation by LemA in order to be active as transcriptional activators.

Abstract: The present invention relates to adenovirus (Ad) E1-complementing cell lines which significantly reduce the presence of replication competent Ad (RCA) and can serve for the large scale production of infectious E1-deleted adenoviral particles that may be used for the treatment human patients as for example in gene therapy. As well the invention relates to a method for the large scale production of recombinant infectious adenoviral particles harboring an exogenous sequence of interest and to a RCA-free stock of infectious adenoviral particles. The invention further relates to a recombinant vector for transfecting an eukaryotic cell line in order to construct Ad E1-complementing cell lines which significantly reduce the presence of RCA and to a method therefor.

Abstract: DNA fragments and methods for obtaining them are disclosed which when put into mammalian cells together with a dominant marker gene are able to form functional centromeres. The sequences can be used to generate probes for these centromeres. Cell lines containing the functional centromeres are also provided. Methods are taught for isolating mammalian centromeric DNA as well as for producing cell lines carrying an excess of mammalian centromeres linked to a dominant selectable marker gene.

Abstract: The invention relates to improved E. coli bacteria with enhanced viability at low temperatures, methods for producing improved bacterial strains capable of enhanced viability at low temperatures, and the isolation and use of genetic material capable of enhancing the viability of bacteria at low temperatures. In addition to the enhanced viability at low temperatures, the bacteria may exhibit enhanced transformation efficiencies after storage at low temperatures. As such, the invention may be used for the insertion of exogenous DNA sequences into the bacteria of the invention.