Abstract: The present invention relates to the use of a class of genes called oil body protein genes that have unique features. The discovery of these features allowed the invention of methods for the production of recombinant proteins wherein a protein of interest can be easily separated from other host cell components. The invention is further exemplified by methods for exploitation of the unique characteristics of the oil body proteins and oil body genes for expression of polypeptides of interest in many organisms, particularly plant seeds. Said polypeptides may include but are not limited to: seed storage proteins, enzymes, bioactive peptides, antibodies and the like. The invention can also be modified to recover recombinant polypeptides fused to oil body proteins from non-plant host cells. Additionally the invention provides a method of using recombinant proteins associated with seed oil bodies released during seed germination for expression of polypeptides that afford protection to seedlings from pathogens.

Abstract: This invention relates to the discovery that toxicity to mustard may be evaluated by diagnostic test means disclosed herein. Upon electrophoretic separation (sodium dodocyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)) of buffered extract of human skin cells (normal human epidermal keratinocytes (NHEK)) which had been exposed to mustard-type chemical compounds a band at approximately 50,000 to 80,000 daltons molecular weight was found. The protein band constitutes a biomarker.

Abstract: The present invention pertains to a novel gene of Bifidobacteria and to the polypeptides encoded thereby. In particular, the present invention pertains to a gene belonging to the Serpin superfamily and its use in the production of bacterial Serpins. Also provides are vectors host cells, and methods for producing bacterial Serpin polynucleotides and/or polypeptides.

Abstract: A process for the production of a protein by cell culture, said process comprising culturing eukaryotic cells which constitutively produce said protein in a medium which comprises an alkanoic acid and/or salt thereof at a maintained concentration of less than 0.1 mM.

Abstract: The present application discloses and claims mutant BACE proteins, recombinant BACE proteins, processes for crystallizing BACE and in particular to its crystal structure and to the uses of this structure in drug discovery.

Abstract: The invention relates to a method for detecting inhibitors or ligands of binding domains, which comprises using a protein which contains at least one catalytic domain and at least one binding domain, incubating said protein with a marker substrate which binds to the catalytic domain of the protein and is converted, with a substrate which can reversibly bind to the catalytic domain and to the binding domain, and with the inhibitor and determining whether the marker substrate is converted by the protein.

Abstract: This invention relates to the androgen-regulated gene, PMEPA1, and proteins encoded by this gene, including variants and analogs thereof. Also provided are other androgen-regulated nucleic acids, a polynucleotide array containing these androgen-regulated nucleic acids, and methods of using the polynucleotide array in the diagnosis and prognosis of prostate cancer.

Abstract: The invention provides genetic suppressor elements that confer upon a cell resistance to one or more chemotherapeutic drug, methods for identifying and obtaining such elements, and methods of using such elements. The invention also provides cloned genes associated with sensitivity to chemotherapeutic drugs.

Abstract: The invention relates to the isolation of the prepro form of cathepsin L, of its leader sequence, of cathepsin L and of the affiliated propeptide from ciliates, in particular Paramecium, to the use of these peptides and to a process for preparing cathepsin L from ciliates.

Abstract: A novel gene was unexpectedly isolated in an attempt to isolate a gene specifically expressed in immortalized cells via antibody screening using an antibody raised against a protein occurring specifically in immortalized cells. The gene thus isolated shares no sequence homology with the entries deposited in the database and was strongly expressed in skeletal muscles and undifferentiated cells. The protein encoded by this gene inhibits the differentiation of myoblasts into myotubes. It also inhibits the transactivation function of p53, a transcription factor involved in tumor suppression.

Abstract: A novel gene was unexpectedly isolated in an attempt to isolate a gene specifically expressed in immortalized cells via antibody screening using an antibody raised against a protein occurring specifically in immortalized cells. The gene thus isolated shares no sequence homology with the entries deposited in the database and was strongly expressed in skeletal muscles and undifferentiated cells. The protein encoded by this gene inhibits the differentiation of myoblasts into myotubes. It also inhibits the transactivation function of p53, a transcription factor involved in tumor suppression.

Abstract: CaM-KIN polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing CaM-KIN polypeptides and polynucleotides in diagnostic assays.

Abstract: The invention provides a nitrile hydratase activation protein participating in activation of nitrile hydratase derived from Pseudonocardia thermophila JCM3095, and a gene sequence encoding the same. Further, the invention provides a recombinant plasmid containing the gene, a recombinant plasmid containing the gene and a nitrile hydratase gene, a transformant strain obtained through transformation with the recombinant plasmid, and a process for producing a corresponding amide compound from a nitrile compound using a culture solution and cells obtained by incubating the transformant strain and treated products of the cells.

Abstract: The present invention is directed to a recombinant enzymes having alcohol and aldehyde dehydrogenase activity which comprises one or mom recombinant polypeptides selected from the group consisting of polypeptides which are identified by SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8 and chimeric recombinant polypeptides that are a chimeric combination of at least two of the following amino acid sequences identified by SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8 and functional derivatives of the polypeptides identified above which contain addition, insertion, deletion and/or substitution of one or more amino acid residues, wherein said enzymatic polypeptides have said alcohol and aldehyde dehydrogenase activity. DNA molecules encoding the recombinant polypeptides, vectors comprising such DNA molecules, host cells transformed by such vectors and processes for the production of such recombinant enzymes are provided.

Abstract: The present invention relates to methods to assay 2-amino-2-deoxy-D-glucose-6-phosphate ketol-isomerase activity. The present invention also relates to methods for drug screening to identify compounds having antimicrobial activity, wherein the compounds have the ability to inhibit the enzymatic activity of a microbial ketol-isomerase. In other embodiments, methods are provided for the identification of compounds that selectively inhibit microbial ketol-isomerase activity compared to the ketol-isomerase activity of the subject being treated for an infection.

Abstract: The present invention provides formaldehyde dehydrogenase genes (FLD) from methylotrophic yeasts. The FLD structural genes confer resistance to formaldehyde and are therefore useful as a selectable marker in methylotrophic yeasts. The FLD promoter sequences are strongly and independently induced by either methanol as sole carbon source (with ammonium sulfate as nitrogen source) or methylamine as sole nitrogen source (with glucose as carbon source). Induction under either methanol, methylamine or both provides levels of heterologous gene expression comparable to those obtained with the commonly used alcohol oxidase I gene promoter (PAOX1). The FLD promoter of Pichia pastoris (PFLD1)is an attractive alternative to PAOX1 for expression of foreign genes in P. pastoris, allowing regulation by carbon (methanol) or nitrogen (methylamine) source within the same expression strain.

Abstract: A novel growth arrest homeobox gene has been discovered and the nucleotide sequences have been determined in both the rat and the human. The expression of the novel homeobox gene inhibits vascular smooth muscle cell growth. The growth arrest homeobox gene hereinafter referred to as the “Gax gene” and its corresponding proteins are useful in the study of vascular smooth muscle cell proliferation and in the treatment of blood vessel diseases that result from excessive smooth muscle cell proliferation, particularly after balloon angioplasty.

Abstract: A novel growth arrest homeobox gene has been discovered and the nucleotide sequences have been determined in both the rat and the human. The expression of the novel homeobox gene inhibits vascular smooth muscle cell growth. The growth arrest homeobox gene hereinafter referred to as the “Gax gene” and its corresponding proteins are useful in the study of vascular smooth muscle cell proliferation and in the treatment of blood vessel diseases that result from excessive smooth muscle cell proliferation, particularly after balloon angioplasty.

Abstract: The present invention relates to the human and murine melanoma inhibitory activity protein-2 (MIA-2) and to the nucleic acids encoding said proteins including a method for producing such proteins by recombinant techniques. The invention also relates to methods for utilizing such proteins for tissue regeneration, tumor treatment including to control the proliferation and differentiation of liver cells in vivo and in vitro. The invention further relates to diagnostic assays including the human and murine antibodies or aptamers and their use in therapy and diagnosis. Further it relates to diagnostic assays applying specific primers for the diagnostic of liver disease.

Abstract: The present invention relates to methods of screening compounds that modulate lipid kinases activity. The invention is more preferably based on the SPA technology to screen compounds that modulate the activity of lipid kinases, in particular membrane lipid kinases, more specifically sphingosine kinases. The invention also includes compositions, products, kits, etc for use in performing the above methods, as well as the compounds identified by said methods, and their uses.

Abstract: The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an &agr;4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.

Abstract: The present invention provides novel isolated ARP/BRP polynucleotides and the membrane-associated or secreted polypeptides encoded by the ARP/BRP polynucleotides. Also provided are ARP and BRP protein multimers. Further provided are the antibodies that immunospecifically bind to a ARP/BRP polypeptide or any derivative, variant, mutant or fragment of the ARP/BRP polypeptide, a ARP/BRP multimer polynucleotide or antibody. The invention additionally provides methods in which the ARP/BRP polypeptide, multimer, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states, e.g. reproductive disorder, as well as to other uses.

Abstract: Provided are DNA sequences encoding cyclin-dependent kinase inhibitor(s) as well as to methods for obtaining the same. Furthermore, vectors comprising said DNA sequences are described, wherein the DNA sequences are operatively linked to regulatory elements allowing expression in prokaryotic and/or eukaryotic host cells. In addition, proteins encoded by said DNA sequences, antibodies to said proteins and methods for their production are provided. Furthermore, regulatory sequences which naturally regulate the expression of the above described DNA sequences are described. Also described is a method for controlling or altering growth characteristics of a plant and/or a plant cell comprising introduction and/or expression of one or more cyclin-dependent kinase inhibitor(s) functional in a plant or parts thereof and/or one or more DNA sequences encoding such proteins.

Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the kinase peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the kinase peptides, and methods of identifying modulators of the kinase peptides.

Abstract: A compound of the formula: wherein R1 is hydrogen, lower alkyl, or optionally substituted arylsulfonyl, or the like, R2 is hydrogen, lower alkyl, or optionally substituted aralkyl, or the like, R3, R4, R5, and R6 each is independently hydrogen, halogen, trihalogenated lower alkyl, or the like, X is hydroxy or optionally substituted amino, Y is COOR (R is hydrogen or an ester residue), optionally substituted aryl, or optionally substituted heteroaryl, has integrase inhibition activity, and is useful as an anti-HIV drug.

Abstract: The present invention is based on the findings that BACE 2, a homolog of &bgr;-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A&bgr;. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE 2 to suppress A&bgr; production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases.

Abstract: The invention is intended to develop a drug capable of directly or indirectly inhibiting the activation of caspase. Specifically, the invention provides a caspase 3 inhibitor comprising a protein comprising the same or substantially the same amino acid sequence as that represented by SEQ ID NO: 1, 2, 3 or 31 or a salt thereof. The protein of the invention, a partial peptide or a salt thereof is useful as a pharmaceutical such as a prophylactic and/or therapeutic agent for AIDS, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, pigmentary retinopathy, cerebellar degeneration, myelodysplastic syndrome, aplastic anemia, sideroblastic anemia, myocardial ischemia, conduction disturbance, chronic cardiac failure, graft-versus-host disease, or congenital or acquired enzymatic defect.

Abstract: Disclosed herein are methods and compositions relating to gene switches that use molecule capable of binding DNA sequences.

Abstract: The present invention relates to the chemically modified genomic sequences of genes associated with tumor suppressor genes and oncogenes, to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of tumor suppressor genes and oncogenes which are directed against the sequence, as well as to a method for ascertaining genetic and/or epigenetic parameters of tumor suppressor genes and oncogenes.

Abstract: A novel growth arrest homeobox gene has been discovered and the nucleotide sequences have been determined in both the rat and the human. The expression of the novel homeobox gene inhibits vascular smooth muscle cell growth. The growth arrest homeobox gene hereinafter referred to as the “Gax gene” and its corresponding proteins are useful in the study of vascular smooth muscle cell proliferation and in the treatment of blood vessel diseases that result from excessive smooth muscle cell proliferation, particularly after balloon angioplasty.

Abstract: The cystatin superfamily includes inhibitors of cysteine proteinases, which function in a protective role with regard to various pathological actions of endogenous proteinases. Zcys6 is a new member of this superfamily.

Abstract: This invention relates to proteins (e.g., peptides) that are capable of facilitating transport of an active agent through a human or animal gastro-intestinal tissue, and derivatives (e.g., fragments) and analogs thereof, and nucleotide sequences coding for said proteins and derivatives. The proteins of the invention have use in facilitating transport of active agents from the lumenal side of the GIT into the systemic blood system, and/or in targeting active agents to the GIT. Thus, for example, by binding (covalently or noncovalently) a protein of the invention to an orally administered drug, the drug can be targeted to specific receptor sites or transport pathways which are known to operate in the human gastrointestinal tract, thus facilitating its absorption into the systemic system.

Abstract: The invention relates to methods for diagnosing Alzheimer's disease from a blood specimen. The method involves incubating a blood sample with a fluorescent probe that interacts with either protein kinase C (PKC) or protein kinase A (PKA), and measuring the fluorescence intensity in different conditions. Variation in the emission spectra data relative to those of the spectra obtained with healthy subjects is a discriminatory factor vis-à-vis Alzheimer's disease. The probes may recognize the catalytic site or the regulator domain of PKC or PKA, and may be coupled to a synthetic organic compound such as bis-indolmaleimide. In one aspect, the probes are lipidic, including probes prepared from phospholipid constituents of a cell membrane. In another aspect, the probes are proteinic or peptide probes of a membrane or cytoskeletal nature. Useful probes include derivatives of substrates for PKC or PKA.

Abstract: The present invention is related to an inhibitor of the inositol polyphosphate 5-phosphatase SHIP2 protein or its encoding nucleotide sequence identified by SEQ ID NO. 1 or of SHIP2 mRNA expression. The present invention is also related to a pharmaceutical composition comprising the inhibitor and an adequate pharmaceutically acceptable carrier or diluent and to a non-human knock-out mammal comprising homozygously or heterozygously a partial or total deletion in its genome of the inositol polyphoshate 5-phosphatase SHIP2 nucleotide sequence.

Abstract: The present invention in the field of biotechnology, provides methods and compositions for providing enhanced growth of, and/or protein production from, cultured mammalian host cells used for the production of commercially useful amounts of expressed proteins, by the use of at least one Bcl2 encoding nucleic acid provided or transcribed in the host cell.

Abstract: An in vitro method to conduct genomic replication of the viral genomes of viruses that utilize RNA-dependent RNA polymerase for replication (RDRP viruses), such as HCV. The method employs a construct comprising the 3′ and 5′ untranslated regions (UTRs) of the viral genome which are operably linked on the 5′ and 3′ ends of a reporter sequence, in antisense orientation, such that when viral replication is occurring within the cell which produces RDRP, the reporter protein will be made. The method of the invention provides an efficient means for measuring genomic replication in RDRP viruses, and also for the rapid screening of compounds for their ability to inhibit genomic replication of RDRP viruses, including the Hepatitis C virus (HCV).

Abstract: IAPL-2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing IAPL-2 polypeptides and polynucleotides in diagnostic assays.

Abstract: The present invention provides a novel protein containing an armadillo repeat, a gene encoding this protein, and production and use thereof. The present inventors identified a gene named ALEX1 encoding a human-derived novel armadillo repeat-containing protein. It was clarified that ALEX1 interacts with several proteins including insulin-degrading enzyme, presenilin-1, and JNK interacting protein 1. This gene shows significantly decreased expression in cancer cells. The protein ALEX1 and the gene encoding this protein are usable as tools in testing for diseases such as cancer and Alzheimer's disease and developing pharmaceutical agents.

Abstract: IAPL-3 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing IAPL-3 polypeptides and polynucleotides in diagnostic assays.

Abstract: BTL.010 is a novel human serine proteinase inhibitor of the Kunitz family that exhibits greater potency towards neutral serine proteinases, particularly leukocyte elastase and proteinase 3 than towards trypsin-like proteinases. BTL.010, or variants thereof, may be employed as therapeutics in diseases such as emphysema, idiopathic pulmonary fibrosis, adult respiratory distress syndrome, cystic fibrosis, rheumatoid arthritis, organ failure, and glomerulonephritis in which uncontrolled proteolysis due to neutral serine proteinase activity results in tissue damage.

Abstract: The invention provides a biological method of producing farnesol or geranylgeraniol.

Abstract: The invention identifies fragments of hsp60 which retain the capability of inducing a pro-inflammatory immune response of cells of the innate immune system. It is further discloses the unexpected finding that smaller peptides derived from these fragments of hsp60 are capable of acting as antagonists of hsp60 insofar as they have the ability to reduce or even prevent the induction of a pro-inflammatory immune response by hsp60 in cells of the innate immune system. It further discloses variants, derivatives and analogs of such peptides, which are capable of acting as antagonists of hsp60 insofar as they have the ability to reduce or prevent the induction of a pro-inflammatory immune response by hsp60 in cells of the immune system. The invention also discloses pharmaceutical compositions comprising such peptide fragments or variants, derivatives and analogs thereof, and their use to prevent or ameliorate inflammatory diseases or disorders.

Abstract: The present invention provides &bgr;-subunit-Associated Regulator of Apoptosis, or BARA, polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, non-human transgenic animals, devices and methods for producing BARA polypeptides. The invention further provides compositions comprising BARA nucleic acids, polypeptides, and fusions or derivatives thereof. The invention further provides methods for treating, preventing, or ameliorating a medical disease, condition, or disorder comprising administering BARA or BARA compositions, as well as methods of diagnosing a pathological condition related to BARA. Still further, the invention provides methods of modulating levels of BARA expression and methods of determining whether a compound stimulates or inhibits BARA polypeptide activity or BARA polypeptide production.

Abstract: A library of mutants of metastable proteins, such as proteinase inhibitors, can be screened for the specific loss of a wild-type capability to bind an antibody, yielding valuable drug-design information which otherwise is unavailable. By this approach, for example, a mutant proteinase inhibitor can be obtained that has the amino acid sequence of a wild-type protein, or an active fragment thereof, save for the presence of one or more mutations in at least one epitope, thereby altering interaction of the mutant with an anti-proteinase inhibitor antibody.

Abstract: The invention relates to proteinase inhibitors and in particular cystatins which have been modified so as to enhance the effectiveness of synthetically manufactured counterparts. The modifications include either site-directed alterations in the structure of the protein and/or the production of hybrid molecules.

Abstract: The present invention relates to a novel I-FLICE-1 or I-FLICE-2 protein which is a novel inhibitor of INFR-1 and CD-95 induced apoptosis. In particular, isolated nucleic acid molecules are provided encoding the human I-FLICE-1 or I-FLICE-2 protein. I-FLICE-1 or I-FLICE-2 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of I-FLICE-1 or I-FLICE-2 activity. Also provided are therapeutic methods for treating diseases and disorders associated with apoptosis.

Abstract: The invention relates to novel nucleic acid and protein sequences from the mung bean Vigna radiata. The nucleic acid sequence, isolated from a bruchid resistant mung bean line, encodes a thionin-like protein with insecticidal properties.

Abstract: The invention provided improved methods of making and producing recombinant proteins in in vitro cultures of host cells using apoptosis inhibitors. The use of one or more apoptosis inhibitors in the methods can reduce apoptosis in the cell cultures and markedly improve yield of the desired recombinant proteins.

Abstract: A process for the preparation in pure form of the protease activating blood clotting factor VII and/or its proenzyme by the use of a chromatography separation processes and/or fractional precipitation is described. The process used may include adsorption on calcium phosphate/hydroxyapatite, a hydrophobic matrix, a chelate matrix, a matrix on which heparin or a substance related to heparin, such as heparin sulfate or dextran sulfate, is immobilized, or a matrix that is coated with an immobilized monoclonal or polyclonal antibody directed against the protein to be isolated, or F(ab) or F(ab)2 fragments of antibodies directed against the protein to be isolated. A pharmaceutical preparation and a reagent are described which contain the said protease and/or its proenzyme.

Abstract: Procedure for the study of the functional activation of leukocytes, platelets and other cells, produced in vivo or induced in vitro, based on the stabilization of cytoplasmic membrane proteins and its detection using quantitative cytometric methods in the absence of any further manipulation of the sample. The procedure includes the sequential incubation of the sample with: 1) either one or a mixture of more than one protease specific inhibitors and, 2) a combination of several fluorochrome-conjugated monoclonal antibodies; to analyze the expression of surface proteins using immunofluorescence methods and quantitative cytometry.