Abstract: This invention relates to a purified isolated DNA fragment of Bacteroides fragilis comprising a sequence for an operon containing two genes designated rprX and rprY. These genes encode two signal transducing regulatory proteins designated RprX and RprY. This invention further relates to the proteins RprX and RprY encoded by the operon. RprX and RprY affect the normal regulation of OmpF by OmpR and EnvZ.

Abstract: Methods for identifying the existence, and optionally the location, of chromosomal aberration(s) in the genome of an organism are disclosed. Intact, chromosomal DNA is hybridized with one or more clones constructed from chromosomal DNA derived from an organism of the same species as the organism to be tested. By identifying the existence of a chromosomal aberration, the susceptibility of an individual to certain disease states can be predicted, and/or the nature of a given disease state can be ascertained with greater certainty.

Abstract: A method of introducing expressible heterologous DNA into Prevotella ruminicola is provided. The method involves conjugal transfer of a shuttle vector comprising the heterologous DNA operatively linked to a promoter functional in P. ruminicola. The invention also provides shuttle vectors for use in the method and P. ruminicola produced by the method. The invention further provides a tetracycline resistance gene of the TetQ class, or fragments thereof that confer tetracycline resistance, and a protein of the TetQ class that provides resistance to tetracycline by protecting ribosomes from tetracycline, or active fragments thereof. Finally, the invention provides a promoter functional in P. ruminicola and an engineered P. ruminicola comprising expressible foreign DNA.

Abstract: Expression vector for expressing the E. coli a polypeptide other than E. coli malate dehydrogenase coded for by a DNA coding sequence. The vector includes a DNA coding for the polypeptide and also includes an initiation codon wherein the DNA sequence is operatively linked to an upstream sequence located upstream of the initiation codon and which is capable of controlling expression of the polypeptide. The upstream sequence consists on the 285 base pair sequence defined by SEQ ID NO:3. A process for expressing a polypeptide by culturing a host strain of E. coli transformed with an expression vector of the invention is also provided.

Abstract: Two novel linear DNA plasmids are described. Also, novel fragments of the plasmids containing the autonomous replication sequence (ARS), and thus capable of self-maintenance as extra chromosomal elements are provided. These novel DNA sequences of the present invention are useful in a vector for self-maintenance in Pichia pastoris and are also useful as plasmid vectors which can be shuttled between yeast and bacteria.

Abstract: The present invention provides human interleukin-8 (IL-8) analogs that are modified in the Glu4 Leu5 Arg6 region, and have a core structure corresponding to the IL-8 (7-51) sequence are provided. These neutrophil binding analogs display altered IL-8 activities that can be exploited for therapeutic and other purposes. Such antagonists include those in which, for example, the Leu5 and/or Arg6 residues are replaced, and in which the Glu4 and/or Leu5 residues are deleted. Also provided are biologically active human interleukin-8 (IL-8) analogs comprising a core sequence that includes IL-8 (1-51), IL-8 (3-51) or IL-8 (4-51). The invention also provides pharmaceutical compositions containing the aforementioned analogs.

Abstract: Heterologous extra-cellular expression of recombinant proteins in soluble functional form is desirable because of the ease associated with purification of the secreted proteins and avoidance of the need for cell extraction and protein refolding procedures. The present invention provides DNA sequences of the naturally-occurring phthalyl amidase gene isolated from Xanthobacter agilis that control transcription, translation, and extra-cellular secretion of proteins in Streptomyces lividans. These DNA sequences can be used in a method for extra-cellular expression of a wide variety of proteins in soluble functional form.

Abstract: Disclosed are methods and compositions for inducing periodontal tissue morphogenesis in a mammal which include a therapeutically effective concentration of a morphogen. The methods and compositions are useful for integrating an implanted tooth in a tooth socket and for inhibiting tissue loss associated with periodontal disease or injury.

Abstract: Methods for producing libraries of diverse nucleotide sequences, and libraries of polypeptides encoded thereby, are provided. The nucleotide sequences comprise a first and a second constant region coupled to a coding sequence, wherein the coding sequence is formed by sequentially coupling nucleotides in a mixture of predetermined proportions of A, T, C, and G based upon a known amino acid profile. Libraries of vectors comprising the diverse nucleotide sequences are also provided. DNA and amino acid sequences encoding the libraries are further provided.

Abstract: The present invention provides therapeutic compositions for the prevention and treatment of pathological conditions involving bone and dental tissue. The present invention also provides a method to promote bone repair and/or growth for the treatment of pathological conditions involving bone tissue, for example, osteoporosis, Paget's disease, osteopetrosis, and periodontal disease and fracture repair, and healing of bone defects by administering FGF-1 to an animal or human in need of such treatment.

Abstract: Disclosed are (1) nucleic acid and amino acid sequences for a novel morphogenic protein; (2) methods for producing and expressing the protein in a biologically active form; and (3) methods for utilizing the protein to induce tissue morphogenesis in a mammal, including methods for increasing a progenitor cell population in a mammal, methods for stimulating progenitor cells to differentiate and maintain their differentiated phenotype in vivo or in vitro, methods for inducing tissue-specific growth in vivo and methods for the replacement of diseased or damaged tissue in vivo.

Abstract: A process for the preparation of oligoribonucleotides of the formula ##STR1## in which n, L, BB, W, T, Y', U, C.sup.1 and C.sup.2 are as defined in the description, by solid-phase synthesis is described, as are intermediates of the oligoribonucleotides.

Abstract: The invention relates to a new tissue plasminogen activator which has strong activity for converting plasminogen into plasmin that degrades the fibrin network of blood clots to form soluble products and therefore is useful as a thrombolytic agent. The invention also relates to a DNA sequence encoding the amino acid sequence for the tissue plasminogen activator, to a process for producing the plasminogen activator, and to a pharmaceutical composition comprising the new tissue plasminogen activator.

Abstract: Methods of designing or modifying protein structure at the protein or genetic level to produce specified amino-termini in vivo or in vitro are described. The methods can be used to alter the metabolic stability and other properties of the protein or, alternatively, to artificially generate authentic amino-termini in proteins produced through artificial means. The methods are based upon the introduction of the use of artificial ubiquitin-protein fusions, and the discovery that the in vivo half-life of a protein is a function of the amino-terminal amino acid of the protein.

Abstract: This invention discloses an expression system which is useful in industrial Bacilli to produce target proteins which include, but are not limited to, alkaline proteases, amylases, cellulases, lipases or other hydrolyases which are normally excreted outside of the host cell.

Abstract: Disclosed is a sugar-modified cytokine which ensures migration of almost all of the dose of cytokine to the liver rapidly after administration to the live body and which can be advantageously used to enhance the effect of liver disease therapy and mitigate side effects.

Abstract: A plasmid vector capable of replicating in a Coryneform bacterial cell bearing a base sequence (a) functioning as an promoter in a Coryneform bacterium, a base sequence (b) functioning as an operator downstream from the base sequence (a), a base sequence (c) functioning as a site for ribosome binding in a Coryneform bacterial cell, a base sequence (d) functioning as a translation initiation codon, and a gene to be expressed which is directly ligated with the base sequence (d) and bearing a gene coding for a repressor protein capable of binding to the base sequence (d) functioning as an operator.

Abstract: Novel expression vectors are provided for expressing a fusion glycoprotein. The fusion glycoprotein contains the N-terminal globular domain of a retroviral env surface protein linked to a selected glycopeptide. Truncation glycoproteins as well as insertion glycoproteins are expressed using the vectors.

Abstract: A gene expression system is used to produce heterologous biologically active proteins, in particular bioactive granulocyte macrophage colony stimulating factor ("GM-CSF"), secreted from a host selected from the Streptomyces genera. The gene expression system includes a regulatory nucleotide sequence linked to a second nucleotide sequence encoding the heterologous protein. The regulatory sequence, encodes a peptide which directs the secretion of the heterologous protein in bioactive form from a host selected from the Streptomyces genera. The regulatory sequence includes a signal sequence and a promoter sequence. The second nucleotide sequence, which encodes GM-CSF or a biologically active derivative of GM-CSF, may be either natural or synthetic. In particular, the invention relates to an expression system for secreting bioactive, non-glycosylated, oxidized, therapeutically useful GM-CSF from a host selected from the Streptomyces genera.

Abstract: Methods are provided for the production of large polypeptides containing repeating sequences of amino acids utilizing biochemical techniques, specifically DNA sequences coding for the expression of the large polypeptides. Systems utilizing exogenous transcriptional and translational regions to control the production of the large polypeptides are also provided.