Abstract: This invention relates to methods and reagents for detecting the presence of symmetrically and asymmetrically methylated arginine residues, either along or in polypeptides, using mass spectrometry. It also provides methods of determining structures of methylated arginine residues, methods of identifying substrates of PMRTs, and methods of conducting proteomic business using any of the suitable methods recited above.

Abstract: The systems and methods described herein relate to nucleic acid probes comprising a a pattern of universal and designate nucleotides, or ‘gapped’ probes, and the use of sets of gapped probes in sequencing by hybridization to determine the sequence of nucleic acid sequences. The inclusion of universal nucleotides in the probes allows for efficient and rapid sequencing of longer nucleotide sequences than can be sequenced using traditional probes. The systems and methods described herein also relate to apparatus for sequencing nucleic acids which include gapped probes, as well as computer systems capable of analyzing data generated using gapped probes in such apparatus.

Abstract: An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. in vitro assays for discovering agents which effect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative and hyperproliferative disorders are provided.

Abstract: The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects at risk chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain morphogens, inducers of those morphogens, or agonists of the corresponding morphogen receptors, or implantation of renal cells induced with those morphogens. The morphogens useful in the invention include osteogenic protein-1 (OP-1) and other members of the OP-1 subfamily of the TGF-&bgr; superfamily of growth factors.

Abstract: The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a novel family of cell-cycle regulatory proteins (“CCR-proteins”). As described herein, this family of proteins includes a polypeptide having an apparent molecular weight of 16 kDa, and a polypeptide having an apparent molecular weight of approximately 15 kDa, each of which can function as an inhibitor of cell-cycle progression, and therefore ultimately of cell growth. Thus, similar to the role of p21 to the p53 checkpoint, the subject CCR-proteins may function coordinately with the cell-cycle regulatory protein, retinoblastoma (RB). Furthermore, the CCR-protein family includes a protein having an apparent molecular weight of 13.5 kDa (hereinafter “p13.5”). The presumptive role of p13.5, like p16 and p15, is in the regulation of the cell-cycle.

Abstract: A hedgehog conjugate which is characterized in that it contains: a) a polypeptide composed of 10 to 30 hydrophobic amino acids and/or amino acids which form transmembrane helices and are positively charged, b) 1 to 4 aliphatic, saturated or unsaturated hydrocarbon residues with a chain length of 10 to 24 C atoms and with a hydrophobic action or c) a hydrophobic thio compound covalently bound to a hedgehog protein and which has a several-fold increased activity and is suitable as a pharmaceutical agent.

Abstract: The present invention relates to rapid, reliable and effective assays for screening and identifying pharmaceutically effective compounds that specifically inhibit the biological activity of fungal GTPase proteins, particularly GTPases involved in cell wall integrity, hyphael formation, and/or other cellular functions critical to pathogenesis. Another aspect of the present invention relates to novel Candida genes and gene products.

Abstract: Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.

Abstract: A method of analyzing a protein, namely determining the amino acid sequence of a protein is described. Trypsin is added to a protein to form a liquid phase mixture of trypsin and the protein. The disulfide linkages of the protein may be reduced and the resulting sulfhydryl groups alkylated either before or after the addition of trypsin. The trypsin is allowed to digest the protein long enough to cleave protein into tryptic fragments. A portion of the digested mixture is ionized by ion evaporation to produce gas phase ions of the tryptic fragments, the gas phase ions being predominantly doubly charged with one charge at each end of the doubly charged ions. The gas phase ions of the tryptic fragments are analyzed by sequentially selecting therefrom ions of a desired mass to charge ratio in a first mass analyzer. The selected ions are fragmented by collision in a second mass analyzer to produce daughter ions, and the daughter ions are then analyzed in a third mass analyzer.

Abstract: The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein comprising contacting a cell sensitive to the hedgehog protein with a steroidal alkaloid, or other small molecule, in a sufficient amount to reduce the sensitivity of the cell to the hedgehog protein.

Abstract: Methods for isolating patched genes, particularly mammalian patched genes, including the mouse and human patched genes, as well as invertebrate patched genes and sequences, are provided. Decreased expression of patched is associated with the occurrence of human cancers, particularly basal cell carcinomas of the skin. The cancers may be familial, having as a component of risk an inherited genetic predisposition, or may be sporadic. The patched and hedgehog genes are useful: in creating transgenic animal models for these human cancers. The patched nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated 15 physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here signalin-related genes, which are involved in signal transduction induced by members of the TGF&bgr; superfamily. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: The present invention relates to compositions and methods for inhibiting fungal growth. In particular, the present invention relates to methods for use as anti-fungal agents of inhibitors, and compositions thereof, of fungal GGPTase. The inhibitors of fungal GGPTase may be peptides, peptidomimetics, or non-peptides.

Abstract: One aspect of the present invention is the synthesis of a binary method that combines variegated peptide display libraries, e.g., in a “display mode”, with soluble secreted peptide libraries, e.g., in a “secretion mode”, to yield a method for the efficient isolation of peptides having a desired biological activity.

Abstract: The invention relates to methods of preparing plasmid pools by growing colonies in discrete wells of a semi-solid or gelatinous medium. This method may facilitate colony collection, reduce colony overgrowth, reduce contamination by adventitious microorganisms, and increase the efficiency of plasmid screening techniques.

Abstract: Constitutive and tissue-specific protein factors which bind to transcriptional regulatory elements of Ig genes (promoter and enhancer) are described. The factors were identified and isolated by an improved assay for protein-DNA binding. Genes encoding factors which positively regulate transcription can be isolated and employed to enhance transription of Ig genes. In particular, NF-kB, the gene encoding NF-kB, IkB and the gene encoding IkB and uses therefor.

Abstract: The invention provides novel polypeptides which are associated with the transcription complex NF-AT, polynucleotides encoding such polypeptides, antibodies which are reactive with such polypeptides, polynucleotide hybridization probes and PCR amplification probes for detecting polynucleotides which encode such polypeptides, transgenes which encode such polypeptides, homologous targeting constructs that encode such polypeptides and/or homologously integrate in or near endogenous genes encoding such polypeptides, nonhuman transgenic animals which comprise functionally disrupted endogenous genes that normally encode such polypeptides, and transgenic nonhuman animals which comprise transgenes encoding such polypeptides.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. In vitro assays for discovering agents which affect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative disorders are provided.

Abstract: The invention provides novel polypeptides which are associated with the transcription complex NF-AT, polynucleotides encoding such polypeptides, antibodies which are reactive with such polypeptides, polynucleotide hybridization probes and PCR amplification probes for detecting polynucleotides which encode such polypeptides, transgenes which encode such polypeptides, homologous targeting constructs that encode such polypeptides and/or homologously integrate in or near endogenous genes encoding such polypeptides, nonhuman transgenic animals which comprise functionally disrupted endogenous genes that normally encode such polypeptides, and transgenic nonhuman animals which comprise transgenes encoding such polypeptides.