Abstract: The present invention is directed to nucleic acids encoding glycosyltransferases, the proteins encoded thereby, and to methods for synthesizing oligosaccharides using the glycosyltransferases of the invention. In particular, the present application is directed to identification a glycosyltransferase locus of Neisseria gonorrhoeae containing five open reading frames for five different glycosyltransferases. The functionally active glycosyltransferases of the invention are characterized by catalyzing reactions such as adding Gal &bgr;1→4 to GlcNAc or Glc; adding GalNAc or GlcNAc &bgr;1→3 to Gal; and adding Gal &agr;1→4 to Gal.

Abstract: Receptor recognition factors exist that recognizes the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor is in one instance, a part of a transcription factor, and also may interact with other transcription factors to cause them to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted with interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by both IFN&agr; and IFN&ggr;. Specific DNA and amino acid sequences for various human and murine receptor recognition factors are provided, as are polypeptide fragments of two of the ISGF-3 genes, and antibodies have also been prepared and tested.

Abstract: Provided herein are variant alleles of a gene encoding a mu opioid receptor, along with cloning vectors for replicating such variant alleles, expressing vectors for expressing the variant alleles to produce variant mu opioid receptors, and antibodies to such variant receptors. Also disclosed are binding characteristics of such variant receptors regarding binding to opioid ligands, and the using of such binding characteristics to diagnose a subjects susceptibility to pain, susceptibility to an addictive disease, selecting an appropriate pain reliever along with a therapeutically effective amount of the reliever to administer to a subject suffering from pain. In addition, diagnostic methods for diagnosing a disease or disorder such as infertility, constipation, diarrhea, decreased immune response relative to a standard, and decreased ability to withstand stress relative to a standard, along with commercial kits for diagnosing such diseases or disorders.

Abstract: The present invention provides a cyclic peptide comprising the structure: wherein X is selected from the group consisting of an amino acid, an amino acid analog, a peptidomimetic and a non-amide isostere, Z is selected from the group consisting of a synthetic amino acid and a biosynthetic amino acid, R is selected from the group consisting of oxygen, nitrogen, sulfur and carbon, n is 0 to 10 and y is 1 to 10. The present invention also provides a cyclic peptide comprising the amino acid sequence of NH2—X(n)—Z—X(y)—COOH and a cyclic bond between the Z residue and COOH other than a thioester bond, wherein X is selected from the group consisting of an amino acid, an amino acid analog, a peptidomimetic and a non-amide isostere, Z is selected from the group consisting of a synthetic amino acid and a biosynthetic amino acid, n is 0 to 10 and y is 1 to 10.

Abstract: The present invention discloses nucleic acids containing transcriptional control elements that are lens transcriptional control elements. One such lens transcriptional control element is exemplified by the control element of the Pax-6 gene. Methods of using these lens transcriptional control elements for drug assays, diagnostics and for identifying transcription factors involved in lens development are also disclosed.

Abstract: Provided herein are variant alleles of a gene encoding a mu opioid receptor, along with cloning vectors for replicating such variant alleles, expressing vectors for expressing the variant alleles to produce variant mu opioid receptors, and antibodies to such variant receptors. Also disclosed are binding characteristics of such variant receptors regarding binding to opioid ligands, and the using of such binding characteristics to diagnose a subjects susceptibility to pain, susceptibility to an addictive disease, selecting an appropriate pain reliever along with a therapeutically effective amount of the reliever to administer to a subject suffering from pain. In addition, diagnostic methods for diagnosing a disease or disorder such as infertility, constipation, diarrhea, decreased immune response relative to a standard, and decreased ability to withstand stress relative to a standard, along with commercial kits for diagnosing such diseases or disorders.

Abstract: The present invention relates to the discovery that the &agr;-dystroglycan receptor is required for Mycobacterium leprae entry into cells, assays for high throughput screening of drugs for use in treatments against leprosy, and methods for studying the role of the receptor in neurodegenerative and musculodegenerative diseases, and the like.

Abstract: The invention relates to an energy homeostasis peptide hormone receptor, and in particular, a second common PACAP/VIP receptor (PACAP/VIP R-2 or R-2B) cDNA expressed in human adipocytes. Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two structurally related peptides with multiple physiological effects. The present receptor recognizes PACAP-38 and VIP with similar affinity and is coupled to the cAMP-mediated signal transduction pathway. Transcripts of the second common PACAP/VIP R-2 receptor are also found in human brain and in a number of peripheral tissues, such as pancreas, muscle, heart, lung, kidney, stomach and at low levels in the liver, while transcripts of PACAP/VIP R-2B are not found in pancreas, stomach or kidney.

Abstract: The present invention provides a crystal containing the N-terminal domain of a STAT protein that is of sufficient quality to perform X-ray crystallographic studies. Methods of preparing the crystals are include in the invention. The present invention further discloses the three-dimensional structure of the crystal. The present invention also provides methods of using the structural information in drug discovery and drug development.

Abstract: Pharmaceutical compositions are provided which comprise neutralizing antibodies to the about 70 kDa mediator produced upon invasive stimulation of macrophages by, e.g., contact with endotoxin.

Abstract: This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing T antigen specific cytotoxic T lymphocytes. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are provided to dendritic cells using a viral vector such as influenza virus which may be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are infected with the vector are then capable of presenting the antigen and inducing cytotoxic T lymphocyte activity or may also be used as vaccines.

Abstract: The present invention provides a vertebrate translation initiation factor (eIF-4AIII), that plays a role in the differentiation of an embryonic cell to an epidermal cell. This translation initiation factor interacts with BMP-4 in a positive regulatory loop. The nucleic acid and amino acid sequences are also disclosed. Also disclosed are methods of using the translation initiation factor, nucleic acids encoding the same, and corresponding antibodies and the like.

Abstract: The present invention is directed to nucleic acids encoding vespid venom enzymes, or fragments thereof, recombinant vectors comprising such nucleic acids, and host cells containing the recombinant vectors. The invention is further directed to expression of such nucleic acids to produce recombinant vespid venom enzymes, or recombinant fragments, derivatives or analogs thereof. Such recombinant products are useful for diagnosis of allergy and for therapeutic treatment of allergy. In specific embodiments, the present invention provides nucleic acids encoding, and complete nucleotide and amino acids sequences for, vespid venom phospholipase, for example, Dolichovespula maculata phospholipase and Vespula vulgaris phospholipase, and vespid venom hyaluronidase, for example, Dolichovespula maculata hyaluronidase.

Abstract: The present invention discloses a unique vertebrate protein, tankyrase that binds to telomeric repeat binding factor 1 (TRF1). Nucleic acids encoding tankyrases are also disclosed. Methods of screening drugs using tankyrase are also included.

Abstract: We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or “priming” phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or “differentiation” phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derive from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.

Abstract: Method is described for sequencing polypeptides by forming peptide ladders comprising a series of polypeptides in which adjacent members of the series vary by one amino acid residue and determining the identity and position of each amino acid in the polypeptide by mass spectroscopy.

Abstract: The present invention is directed to the identification of mutant strains of methicillin resistant bacteria, in particular methicillin resistant Staphylococcus aureus, to identify the characteristics of such bacteria and develop drugs that can reverse, inhibit, or reduce bacterial resistance to beta lactam antibiotics, e.g., methicillin. The invention particularly relates to identification of a novel mutant strain of methicillin resistant S. aureus that manifests a unique phenotype. Accordingly, the invention provides for methods of treatment and corresponding pharmaceutical compositions for treating bacterial, particularly staphylococcal, infections.

Abstract: Isolated nucleic acid molecules encoding Thyroid Receptor-Associated Proteins (TRAPS) are provided. TRAPS are members of protein complexes that bind to nuclear hormone receptors in a ligand-dependent manner so that the receptor, upon activation by a corresponding hormone, regulates the transcription of a particular gene. Also provided are methods of replicating and expressing such isolated nucleic acid molecules, pharmaceutical compositions comprising TRAPS, and methods of modulating gene expression via administration of therapeutically effective amounts of such pharmaceutical compositions.

Abstract: The invention relates to bacterial choline binding proteins (CBPs) which bind choline. Such proteins are particularly desirable for vaccines against appropriate strains of Gram positive bacteria, particularly streptococcus, and more particularly pneumococcus. Also provided are DNA sequences encoding the bacterial choline binding proteins or fragment thereof, antibodies to the bacterial choline binding proteins, pharmaceutical compositions comprising the bacterial choline binding proteins, antibodies to the bacterial choline binding proteins suitable for use in passive immunization, and small molecule inhibitors of choline binding protein mediated adhesion. Methods for diagnosing the presence of the bacterial choline binding protein, or of the bacteria, are also provided. In a specific embodiment, a streptococcal choline binding protein is an enolase, which demonstrates strong affinity for fibronectin.

Abstract: The invention is directed to constitutively active Stat proteins and methods for their preparation. The modified Stat proteins have at least one cysteine residue which may interact with the corresponding cysteine residue on another modified Stat protein to form a dimer. The constitutively active Stat proteins are capable of binding to DNA and activating transcription in the absence of tyrosine phosphorylation. Cell lines expressing the modified Stat protein exhibit a transformed phenotype and are capable of forming tumors in nude mice. Methods are describe utilizing the modified Stat proteins of the invention in the absence and presence of tyrosine phosphorylation in identifying agents capable of modulating Stat protein dimerization, transcriptional activity, and cellular transformation in vitro and in vivo. The invention is also directed to polynucleotides encoding modified, constitutively active Stat proteins.