Abstract: The present invention is based at least in part on the discovery of polymorphisms within the 5-lipoxygenase gene which are included in a haplotype. Accordingly, the invention provides nucleic acid molecules having a nucleotide sequence of an allelic variant of a 5-LO gene. The invention also provides methods for identifying specific alleles of polymorphic regions of a 5-LO gene, methods for determining whether a patient has a more or less severe phenotype of an inflammatory disease or disorder such as asthma, methods for determining whether a patient will be more or less responsive to treatment with 5′LO inhibitors, forensic methods based on detection of polymorphisms within the 5-LO gene, and kits for performing such methods.

Abstract: Compounds which are active against viruses have the following Formulas: wherein B is a purine or pyrimidine heterocyclic ring and is preferably selected from the group consisting of 6-aminopurine (adenine), 2,6-diaminopurine, 2-amino-6-azidopurine, 2-amino-6-cyclopropylaminopurine, 6-hydroxypurine (hypoxanthine), 2-amino-6-halo substituted purines, 2-amino-6-alkoxy substituted purines, 2-amino-6-hydroxypurine (guanine), 3-deazapurines, 7-deaza-purines, 8-azapurines, cytosine, 5-halo substituted cytosines, 5-alkyl substituted cytosines, thymine, uracil and 6-azapyrimidines; X is O; and, R1 and R2 are alkyl or aryl groups. The compounds of the present invention also include the R- and S-enantiomers of the above compounds. The R1X and/or R2X can also be amino acid residues with X as NH.

Abstract: A method of making a set of labelled compounds by the use of a preferably particulate support, comprises dividing the support into lots, performing a different chemical reaction on each lot of the support, e.g. to couple a chemical moiety to that lot of the support, tagging a fraction of each lot of the support with a different label, and combining the said lots of the support. The steps are repeated several times, preferably to build up oligomer molecules carrying labels which identify the nature and position of a monomer unit of the oligomer, and which are releasable from the support. Preferred labels, which are releasable from the compounds by cleavage to provide charged groups for analysis by mass spectrometry, are groups of the trityl (trimethylphenyl) family. Also claimed are libraries of these labels and their use in assays and nucleic acid analysis methods.

Abstract: The present invention is directed to novel exocytotic polypeptides, such as Exo1 and Exo2 polypeptides and related molecules, which have an inhibitory effect on exocytosis and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided by the present invention are method for identifying novel compositions which mediate exocytotic polypeptide bioactivity, and the use of such compositions in diagnosis and treatment of disease.

Abstract: The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e.g., brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The present invention relates to novel SH3 domain binding protein, referred to herein a DEF polypeptides. The DEF polypeptides comprise several motifs including a src SH3 consensus binding sequence, four ankyrin repeats, one zinc finger domain and six copies of a proline-rich tandem repeat. DEF polypeptides may function as mediators of SH3 domain-dependent signal transduction pathways and, thus may mediate multiple signaling events such as cellular gene expression, cytoskeletal architecture, protein trafficking and endocytosis, cell adhesion, migration, proliferation and differentiation. Described herein are isolated and antisense nucleic acids molecules, recombinant expression vectors, host cells and non-human transgenic animals containing an insertion or a disruption of the DEF gene.

Abstract: A method for inhibiting proliferation of a PPAR &ggr;-responsive hyperproliferative cell which comprises the step of contacting the cell with (I) an inhibitory amount of a PPAR&ggr; agonist and (II) a MAP kinase inhibitor is disclosed. A method for treating or prophylactically preventing in an animal subject a disorder characterized by unwanted proliferation of PPAR&ggr;-responsive hyperproliferative cells which comprises administering to the subject (I) an inhibitory amount of a PPAR&ggr; agonist and (II) a MAP kinase inhibitor is also disclosed. Pharmaceutical compositions comprising a therapeutically effective amount of a PPAR&ggr; agonist and a MAP kinase inhibitor are disclosed for use in the methods.

Abstract: Novel TRL polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length TRL proteins, the invention further provides isolated TRL fusion proteins, antigenic peptides and anti-TRL antibodies. The invention also provides TRL nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a TRL gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.