Abstract: Chemically inducible promoters are described that may be used to transform plants, including tobacco and lettuce, with genes which are easily regulatable by adding the plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoters described are ones that are inducible by a glucocorticoid or estrogen which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt, CKI1, or knotted1, to induce shoot formation in the presence of an appropriate inducer. The promoters may be used with genes which induce somatic embryos such as Lec1 or SERK to prepare somatic embryos which can be grown into seedlings and then into plants. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.

Abstract: Modulators of weight, including, for example, two isoforms of murine and human ob polypeptides, are provided, as well as diagnostic and therapeutic uses and methods comprising such. Also provided are nucleotide sequences, degenerate variations thereof, and proteins expressed by such. Such materials are useful, for example, as molecular probes, as primers for polymerase chain reaction (PCR) amplification, as well as for the generation of antibodies. Also provided are vectors comprising such nucleotide sequences, including bacterial, insect, and mammalian expression vectors, which nucleotide sequences are operatively associated with an expression control sequence. Cells transformed or transfected with such vectors, and the use of such in the preparation of disclosed modulators, are also provided.

Abstract: The invention relates to the discovery that the Claudin-1 protein functions as a co-receptor for entry of HCV into cells. Methods of inhibiting, preventing or mitigating HCV infections by inhibiting HCV interactions with Claudin-1 are provided. Methods of identifying agents or compounds that interfere with HCV interactions with Claudin-1 are also provided. Finally, useful kits, cell culture compositions, agents, and compounds related to the inhibition of HCV interactions with Claudin-1 are also disclosed.

Abstract: The present invention relates to human Rif1 (hRif1) nucleic acid sequences and human Rif1 amino acid sequences encoded therefrom. The invention also encompasses antibodies that are immunologically specific for human Rif1 polypeptides. Also included in the present invention are methods directed to detecting Rif1 foci formed in response to various treatments that induce DNA damage. The formation of foci comprising Rif1 in response to DNA damage serves as a positive indicator of the presence of wild type ATM kinase activity in a cell, whereas the absence of detectable Rif1 foci under such circumstances serves to identify a cell with reduced ATM kinase activity. Modulators of ATM kinase activity and/or Rif1 activity and methods for identifying such modulators are also included in the present invention.

Abstract: The present invention provides a crystallized N-terminal domain of an NS5A protein of hepatitis C virus, methods of producing the same and methods of use thereof. The present invention also relates to structural elements of the N-terminal domain of hepatitis C virus NS5A protein, and methods of inhibiting hepatitis C virus infection, replication and/or pathogenesis, by interacting with the same.

Abstract: The present invention relates to the identification of a subunit vaccine to prevent or treat infection of Epstein Barr Virus. In particular, EBNA-1 was identified as a vaccine antigen. In a specific embodiment, a purified protein corresponding to EBNA-1 elicited a strong CD4+ T cell response. The responsive CD4+ T cell are primarily TH1 in function. EBNA-1 is an attractive candidate for a protective vaccine against EBV, and for immunotherapy of EBV infection and neoplasms, particularly with dendritic cells charged with EBNA-1.

Abstract: The present invention provides a method for identifying an agent to be tested for an ability to treat a psychotic disorder in a patient in need of such treatment. The invention provides a method for screening candidate drugs for anti-psychotic drug activity, preferably atypical anti-psychotic activity, comprising contacting cells or tissues with a candidate drug, determining levels of phosphorylation of the intracellular signaling proteins, DARPP-32, ERK1, ERK2 and CREB, in said cells or tissues and determining the pattern of the levels of phosphorylation of the proteins. The pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB is, in certain embodiments, compared with the pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB in the presence of an atypical anti-psychotic drug.

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 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 to 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. Methods of preparation including a cyclization protocol, and methods of use of the cyclic peptides of the invention are also disclosed.

Abstract: The present invention is related to enhancing the function of anti-tumor antibodies by regulating Fc?RIIB-mediated activity. In particular, disrupting SHIP activation by Fc?RIIB enhances cytotoxicity elicited by a therapeutic antibody in vivo in a human. The invention further provides an antibody, e.g., an anti-tumor antibody, with a variant Fc region that results in binding of the antibody to Fc?RIIB with reduced affinity. A variety of transgenic mouse models demonstrate that the inhibiting Fc?RIIB molecule is a potent regulator of cytotoxicity in vivo.

Abstract: The present invention relates to peptides and methods of inhibiting fusion between the virion envelope of Flaviviruses and membranes of the target cell, the process that delivers the viral genome into the cell cytoplasm. The invention provides for methods which employ peptides or peptide derivatives to inhibit Flavivirus:cell fusion. The present invention is based in part on the discovery that E1 envelope glycoprotein of hepaciviruses and E2 envelope glycoprotein of pestivirus have previously undescribed structures, truncated class II fusion proteins. The present invention provides peptides and methods of treatment and prophylaxis of diseases induced by Flaviviruses.

Abstract: The present invention describes methods of producing milligram quantities of three forms of purified Stat1 protein from recombinant DNA constructs. In addition, the Stat proteins may be isolated in their phosphorylated or nonphosphorylated forms (Tyr 701). The proteins can be produced in baculovirus infected insect cells, or E. coli. A compact domain in the amino terminus of Stat1? was isolated and found to enhance DNA binding due to its ability to interact with a neighboring Stat protein. A relatively protease-resistant recombinant truncated form of the Stat protein was isolated in 40-50 mg quantities. Purification of the Stat proteins were performed after modifying specific cysteine residues of the Stat proteins to prevent aggregation. Activated EGF-receptor partially purified from membranes by immunoprecipitation was shown to be capable of in vitro catalysis of the phosphorylation of the tyrosine residue of Stat1 known to be phosphorylated in vivo.

Abstract: The invention relates to isolated nucleic acid molecules comprising the sequence of a DNA virus microRNA. In another embodiment, the invention relates to single stranded DNA virus microRNA molecules. In yet another embodiment, the invention relates to single stranded anti-DNA virus microRNA molecules.

Abstract: A composition of matter suitable for use in identifying chemical compounds that bind to voltage-dependent ion channel proteins, the composition comprising a screening protein that comprises an ion channel voltage sensor domain of the ion channel protein immobilized on a solid support.

Abstract: The present invention provides methods and compositions for modulating the activity of phosphodiesterase 1B (PDE1B) in intracellular signaling pathways, including but not limited to, dopamine D1 intracellular signaling pathways. The invention also provides methods and compositions for modulating the activities of intracellular signaling molecules, including, but not limited to, DARPP-32 and GluR1 AMPA receptor, via modulation of PDE1B. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate PDE1B activity. The invention also provides methods of treating or ameliorating the symptoms of a disorder, including but not limited to a PDE1B-related disorder or a dopamine D1 receptor intracellular signaling pathway disorder, by administering a modulator of PDE1B, preferably, but not limited to, an inhibitor of PDE1B or an agent that decreases the production of PDE1B.

Abstract: The present disclosure relates to methods, compositions and articles of manufacture useful for the treatment of Bacillus anthracis and B. cereus bacteria and spores, and related conditions. The disclosure further relates to methods and compositions for the identification of a phage associated lytic enzyme to rapidly and specifically detect and kill Bacillus anthracis and other bacteria. Related articles of manufacture, methods of degrading spores and methods of treatment of infections or bacteria populations of, or subjects exposed to or at risk for exposure to, Bacillus anthracis are also provided.

Abstract: A method of modulating immune response in an animal is disclosed. Such a method interacting the immature dendritic cells from the animal with an antigen ex vivo so that the immature dendritic cells present the antigen on their surfaces, inducing maturation of the immature dendritic cells ex vivo, and contacting the mature dendritic cells ex vivo with a modulator comprising TRANCE, conservative variants thereof, fragments thereof, analogs or derivatives thereof, or a fusion protein comprising the amino acid sequence of TRANCE, conservative variants thereof, or fragments thereof. After contacting the modulator ex vivo, the mature dendritic cells are introduced into the animal. As a result, immune response in the animal towards the antigen is modulated relative to the immune response against the antigen in an animal in which dendritic cells did not interact with the antigen ex vivo, and did not contact a modulator ex vivo.

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 invention relates to isolated DNA or RNA molecules comprising at least ten contiguous bases having a sequence in a pancreatic islet microRNA. In another embodiment, the invention relates to isolated single stranded pancreatic islet microRNA molecules or anti-pancreatic islet microRNA molecules.

Abstract: This invention provides for novel methods of identifying covalent modifications of an amino acid residue in a polypeptide chain by detecting mass differences.