Abstract: Synthetic polypeptides from the conserved exposed region of streptococcal M protein are useful to prepare vaccines for oral or intranasal administration which will protect against streptococcal infection.

Abstract: The present invention relates to a novel nucleotide sequence encoding a telomeric protein which binds a repeat region of telomeric sequences, and to the protein encoded thereby. Also included within the invention are expression vectors for the production of the telomeric protein and host cells transformed with the nucleotide sequence. In addition, antibodies, probes and antagonists specific for the telomeric protein are contemplated. Methods of identifying antagonists of the telomeric protein, diagnostic methods of identifying the telomeric protein in a sample, and therapeutic uses of the telomeric protein, particularly in the treatment of aging and cancer, are also contemplated.

Abstract: The present invention is directed to a method for amplifying or sequencing a nucleic acid molecule with a three component polymerase comprising a DNA polymerase component, a sliding clamp component, and a clamp loader component.

Abstract: The present invention is a method for accurately comparing the levels of cellular components, such as proteins, present in samples which differ in some respect from each other using mass spectroscopy and isotopic labeling. A first sample of biological matter, such as cells, is cultured in a first medium and a second sample of the same biological matter is cultured in a second medium, wherein at least one isotope in the second medium has a different abundance than the abundance of the same isotope in the first medium. One of the samples is modulated, such as by treatment with a bacteria, a virus, a drug, hormone, a chemical or an environmental stimulus. The samples are combined and at least one protein is removed. The removed protein is subjected to mass spectroscopy to develop a mass spectrum. A ratio is computed between the peak intensities of at least one closely spaced pair of peaks to determine the relative abundance of the protein in each sample.

Abstract: A method and apparatus for increasing the signal-to-noise ratio in a range of mass-to-charge ratios of a mass spectrum. Initially ions of interest and background ions having mass-to-charge ratios within the range of mass-to-charge ratios are generated. The ions of interest and the background ions are then subjected to an activation energy sufficient to cause dissociation of background ions to an extent greater than the dissociation of the ions of interest. The dissociation of the background ions causes the background ions to have mass-to-charge ratios that fall outside of the range of mass-to-charge ratios. The mass-to-charge ratios of the ions of interest are then detected.

Abstract: Disclosed are recombinant hybrid proteins having at least one antigenic peptide sequence introduced into a scaffold protein that retain a native conformation. Also disclosed are recombinant nucleic acids and vectors encoding the hybrid proteins. The hybrid proteins retain immunogenicity but exhibit reduced allergenicity. The hybrid proteins are therefore particularly useful for therapeutic treatment of allergy.

Abstract: The present invention relates to the identification in vertebrate animals, including humans, of an ion channel which is involved in osmoregulation and mechanoreception. This ion channel, named VR-OAC, functions as a cation channel which is activated by osmotic and mechanical stimulation. In particular, the present invention relates to the broad applications of VR-OAC that capitalize on its newly discovered properties and activities, including both diagnostic and therapeutic methodologies. The invention further relates to methods for using the receptor therapeutically, such as polypeptide or gene therapy, diagnostically. and to methods and assays for identification and screening of VR-OAC analogs, agonists or antagonists and uses thereof.

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: The invention relates to a method of delivering exogenous DNA to a target cell of the mammalian central nervous system using an adeno-associated virus (AAV)-derived vector. Also included in the invention are the AAV-derived vectors containing exogenous DNA which encodes a protein or proteins which prevent or treat nervous system disease, and a method of prevent or treating such disease.

Abstract: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved “knuckle” of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues.

Abstract: The present invention concerns a method of treating sepsis comprising administering a therapeutically effective amount of anti-CD14 antibody molecules. A therapeutic composition comprising anti-CD14 antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

Abstract: The present invention relates to methods and compositions for modulating activity of a TRANCE receptor, including the modulation of TRANCE signaling activity. In particular, the invention provides screening methods by which novel modulators of TRANCE signaling may be identified, including TRANCE inhibitors, agonists and antagonists. The invention also relates to the identification of one or more specific pathways for osteoclast surivival, and the manipulation of this pathway (e.g., using a TRANCE modulator of the invention). Such manipulation may provide strategies for treating osteoclast-related diseases such as osteoporosis and osteopetrosis.

Abstract: Recombinant expression systems for the production of proteins, and particularly a system for rapidly generating recombinant silkworm baculoviruses. Bombyx mori nuclear polyhedrosis virus (BmNPV) with an efficiency approaching 100% has been developed. In a specific example, the vector of the invention was used to generate expression of a FLAG-epitope tagged HIV tat interacting protein of 30 kDa (f-TIP30) in BmN cells and silkworm larvae.

Abstract: A method of efficiently sequencing multiple exons from complex genomic DNAs is disclosed. The methodology includes the use of bacterial and bacteriophage-derived artificial chromosomes (BBPACS) in novel gene trapping protocols. Targeted gene trapping by homologous recombination, and random gene trapping with the use of a transposon system are exemplified. Included in the invention are methods of preparing a gene map from BBPAC contigs, the resulting gene maps, methods of constructing a cDNA library from BBPAC contigs, and the resulting cDNA libraries.

Abstract: The bZIP transcription factor ABI5 is shown to confer an enhanced response to exogenous abscisic acid during germination, seedling establishment and subsequent vegetative growth of plants. ABI5 is necessary, but not sufficient, to maintain germinated embryos in a quiescent state, abscisic acid also being required for maintaining the quiescent state. ABI5 production is enhanced by stress including high salt and drought. This protects plants from drought. Plants which overexpress ABI5 are hypersensitive to abscisic acid and retain water more efficiently than wild-type plants.

Abstract: The present invention discloses the identity of the first enzyme that has been demonstrated to be involved in maintaining circadian rhythms. This enzyme, the Drosophila DOUBLETIME protein is also shown to be an ortholog of human casein kinase-1&egr;. In addition, a variant of this enzyme is shown to be cause of the hamster tau mutant phenotype. Thus the present invention also relates to variants of DOUBLETIME, and their nucleic acid and amino acid sequences. The present invention further provides methods of using these variants in drug assays and diagnostics.

Abstract: A method for producing proliferating cultures of dendritic cell precursors is provided. Also provided is a method for producing mature dendritic cells in culture from the proliferating dendritic cell precursors. The cultures of mature dendritic cells provide an effective means of producing novel T cell dependent antigens comprised of dendritic cell modified antigens or dendritic cells pulsed with antigen, including particulates, which antigen is processed and expressed on the antigen-activated dendritic cell. The novel antigens of the invention may be used as immunogens for vaccines or for the treatment of disease. These antigens may also be used to treat autoimmune diseases such as juvenile diabetes and multiple sclerosis.

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: 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 of the diagnostic and therapeutic uses to such modulators. 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. The present invention further provides nucleic acid molecules for use as molecular probes, or as primers for polymerase chain reaction (PCR) amplification, i.e.

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.