Abstract: The present invention provides the structural determination of a bromodomain determined by NMR spectroscopy. The present invention also provides binding partners for the bromodomain. The present invention further provides the structural determination of the Tat-P/CAF binding complex determined by NMR spectroscopy. In addition, the present invention provides methodology for related drug discovery using high throughput drug screening or structure based rational drug design using the three-dimensional data.

Abstract: The present invention provides isolated cells that comprise, integrated into the genome of the cell, a transcription-competent immunodeficiency virus or a transcription-competent immunodeficiency virus-based retroviral vector. Under basal in vitro culture conditions, the immunodeficiency virus is latent, and the expression of the latent immunodeficiency virus can be reactivated. The invention farther provides methods of making a subject cell. The invention further provides screening methods for identifying agents that activate a latent immunodeficiency virus; and screening method for identifying agents that block reactivation of latent immunodeficiency virus expression in response to T cell activation signals. The invention further provides agents identified in the subject screening assays. The invention further provides methods of treating an immunodeficiency virus infection.

Abstract: This invention discloses the first cellular acetylated substrate protein of SIRT3, Acetyl-CoA synthetase 2 (AceCS2), which is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at lysine 642 (Lys642) in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the acetyl-CoA synthetase activity of AceCS2. Thus, a mammalian sirtuin directly controls the activity of a metabolic enzyme via reversible lysine acetylation. Modulators of the acetylation status or the activity of AceCS2 are useful for the treatment of pathological conditions, such as type II diabetes, hypercholesterolemia, hyperlipidemia, and obesity.

Abstract: The present invention provides nucleic acid molecules that encode histone deacetylase, as well as recombinant vectors and host cells that include the subject nucleic acid molecules. Also provided are histone deacetylase polypeptide compositions. The histone deacteylase nucleic acid molecules are useful in a variety of diagnostic and therapeutic applications, which are also provided.

Abstract: The present invention provides compositions, including immunogenic compositions, comprising acetylated Tat protein of an immunodeficiency virus. The present invention further provides antibodies that specifically bind an acetylated Tat polypeptide. The present invention further provides methods of inducing an immune response to an immunodeficiency virus Tat protein in an individual. The present invention further provides methods of inhibiting transcriptional activation of an immunodeficiency virus in a cell of an individual.

Abstract: The present invention provides isolated apolipoprotein E (apoE) stable folding intermediates. The invention further provides methods for identifying compounds that alter the structure or level or activity of an apoE stable folding intermediate, as well as methods of inhibiting the formation or activity of stable folding intermediates of apoE. The invention further provides methods for reducing the level and/or activity of an apoE stable folding intermediate, and methods for treating disorders relating to apoE4 in a subject.

Abstract: The present invention provides nucleic acid molecules that encode histone deacetylase, as well as recombinant vectors and host cells that include the subject nucleic acid molecules. Also provided are histone deacetylase polypeptide compositions. The histone deacteylase nucleic acid molecules are useful in a variety of diagnostic and therapeutic applications, which are also provided.

Abstract: The present invention relates to screening methods that make use of a histone deacetylase interacting with a myosin phosphatase for the identification of novel therapeutics useful for inhibiting or inducing apoptosis and for the treatment of pathological conditions, such as smooth muscle cell disorder, cardiac hypertrophy or asthma. Also disclosed are methods for inhibiting or inducing apoptosis and for treatment of a pathological condition by administering to a mammal a therapeutically effective amount of a compound that inhibits or increases the dephosphorylation of a histone deacetylase by a myosin phosphatase or inhibits or increases the binding of a histone deacetylase to a myosin phosphatase.

Abstract: The present invention provides a method of detecting antigen-specific T lymphocytes in a sample. The present invention further provides kits and systems for detecting antigen-specific T lymphocytes in a sample.

Abstract: The present invention provides methods of detecting an amyloid peptide-related neurological disorder in an individual; and methods for staging an amyloid peptide-related neurological disorder in an individual. The methods involve detecting a level of a calcium-responsive gene product, such as calbindin, in a hippocampal neuron, especially a granule cell of the dentate gyrus. The invention further provides identifying an agent that treats an amyloid peptide-related neurological disorder, as well as agents identified by the methods.

Abstract: The present invention features methods and compositions relating to a virion-based fusion assay for detection of infection of a target cell by an enveloped retroviral virion such as HIV. The assay uses virions containing a chimeric viral protein comprising a viral accessory polypeptide (such as Vpr) fused to a reporter polypeptide (such as beta-lactamase). Fusion of the virion with a target cell membrane results in intracellular delivery of the chimeric protein to the target cell, which in turn provides for detection of a detectable signal mediated by the reporter polypeptide portion of the chimeric polypeptide. Significant detectable signal is only detected following intracellular delivery of the chimeric viral protein, thus providing for detection of productive viral entry to the exclusion of non-productive, endocytic entry of virions into the cell.

Abstract: The present invention provides methods of detecting specific lysis of a cell by a lytic agent. The methods generally involve contacting a labeled target cell with a lytic agent; and detecting fluorescence in the target cell. The target cells are labeled with two fluorescent labels: a first fluorescent label that labels the plasma membrane; and a second fluorescent label that labels the cytosol. Release of the cytosolic label from the target cell indicates that the target cell has been lysed. The invention further provides methods of detecting the presence in a sample of a cell that specifically lyses a target cell. The invention further provides methods of detecting the presence in a sample of an antibody that specifically lyses a target cell. The methods are useful in a variety of applications.

Abstract: The present invention provides screening methods for identifying a compound that induces loss of the lentiviral protein Vpr; screening methods for identifying compounds that inhibit the peptidyl-prolyl cis/trans isomerase (PPIase) activity of a protein that catalyzes cis-trans isomerization of cis-peptidylprolyl bonds in Vpr; and compounds identified by the screening methods. The compounds are useful for treating a lentiviral infection. The present invention further provides methods of inducing loss of the lentiviral protein Vpr; methods of inhibiting lentivirus viral replication; and methods of treating a lentivirus infection in an individual. The methods generally involve administering to an individual infected with the lentivirus an effective amount of a compound that induces Vpr loss and/or that inhibits PPIase activity of a protein that catalyzes cis-trans isomerization of cis-peptidylprolyl bonds in Vpr.

Abstract: The invention pertains to synthetic (s) peptides derived from the viral regulatory protein R (Vpr) of the human immunodeficiency virus type 1 (HIV-1), particularly the chemical synthesis of the 96 amino acid full length Vpr protein (sVpr1-96), of a 47 amino acid long N-terminal (sVpr1-47), of a 49 amino acid long C-terminal fragment (sVpr48-96) as well as fragments thereof (sVpr1-20 and sVpr21-40) and further approximately 15 amino acid long fragments of sVpr1-96. As fragments or full length products of the HIV-1 regulatory protein, those products are used in biological assays, for molecular and structural characterization of Vpr and domains thereof, as well as for the development of anti-Vpr antibodies directed against Vpr peptide sequences.

Abstract: The present invention provides methods of detecting specific lysis of a cell by a lytic agent. The methods generally involve contacting a labeled target cell with a lytic agent; and detecting fluorescence in the target cell. The target cells are labeled with two fluorescent labels: a first fluorescent label that labels the plasma membrane; and a second fluorescent label that labels the cytosol. Release of the cytosolic label from the target cell indicates that the target cell has been lysed. The invention further provides methods of detecting the presence in a sample of a cell that specifically lyses a target cell. The invention further provides methods of detecting the presence in a sample of an antibody that specifically lyses a target cell. The methods are useful in a variety of applications.

Abstract: The present invention features transgenic rodent models for HIV, wherein the transgenic rodent or transgenic rodent cell has incorporated into its genome genes encoding a human CD4 receptor and a human chemokine receptor. In particular the invention relates to transgenic rats, or mice characterized by being susceptible to infection with HIV, capable of expressing HIV structural genes, or HIV replication. The transgenic rodent or rodent cell of this invention is useful for studying the molecular basis of HIV infection, replication and pathogenicity, as well as for the testing of agents for new antiviral or vaccine strategies.

Abstract: Methods and compositions for the inhibition of NF-&kgr;B activation are disclosed.