Abstract: The invention relates to the field of longevity enhancement. More particularly, the invention provides compositions and methods relating to modulation of mitochondrial function. In certain embodiments, the invention provides methods and related compositions for the enhancement of longevity in an animal, comprising inhibition of one or more electron transport chain components, such as cco-1 and homologs thereof, in a tissue-specific manner in the animal.

Abstract: This disclosure concerns compositions and methods for improving the incorporation of unnatural amino acids (UAAs) into proteins in eukaryotic cells. It is shown herein that mutation of a prokaryotic tRNA synthetase to increase the interaction with the corresponding tRNA anticodon region results in increased UAA incorporation efficiency in mammalian cells.

Abstract: In accordance with the present invention, a novel aromatic prenyltransferase, Orf2 from Streptomyces sp. strain CL190, involved in naphterpin biosynthesis has been identified and the structure thereof elucidated. This prenyltransferase catalyzes the formation of a C—C bond between a prenyl group and a compound containing an aromatic nucleus, and also displays C—O bond formation activity. Numerous crystallographic structures of the prenyltransferase have been solved and refined, e.g., (1) prenyltransferase complexed with a buffer molecule (TAPS), (2) prenyltransferase as a binary complex with geranyl diphosphate (GPP) and Mg2+, and prenyltransferase as ternary complexes with a non-hydrolyzable substrate analogue, geranyl S-thiolodiphosphate (GSPP) and either (3) 1,6-dihydroxynaphthalene (1,6-DHN), or (4) flaviolin (i.e., 2,5,7-trihydroxy-1,4-naphthoquinone, which is the oxidized product of 1,3,6,8-tetrahydroxynaphthalene (THN)). These structures have been solved and refined to 1.5 ?, 2.25 ?, 1.95 ? and 2.

Abstract: TZP proteins and method of their use for improving plant characteristics are disclosed.

Abstract: Provided herein are methods for, inter alia, identifying new therapeutic agents using human cell-based models.

Abstract: This disclosure ascribes new functions to derivatives of tetralin, anthraquinone, naphthylamine, tri-amino-pyrimidine, xanthen-3-one, and/or cinnamic acid (including, for example, NSC270718R, NSC117285R, NSC170008Y, NSC306711P, NSC119913X, NSC119915Z, NSC119911V, NSC119910U, NSC128437O, NSC125908P, NSC9600Q, or NSC13778J, each obtained from the Structure Diversity Set, National Institutes of Health, National Cancer Institute, Developmental Therapeutics Program). These compounds are shown to be effective inhibitors of viral essential protein kinases (such as poxvirus B1 and/or F10 protein kinases). Exemplary chemical structures for viral protein kinase (VPK) inhibitors are provided, as are methods of using such compounds, for instance, to inhibit VPK activity and/or poxvirus growth, and/or for the treatment of poxvirus infection. Also provided are pharmaceutical compositions including disclosed VPK inhibitors.

Abstract: Ubiquitin ligase wwp-1 and ubiquitin conjugating enzyme ubc-18 are identified in nematodes as mediators of dietary restriction induced longevity and therefore as targets for modulation of lifespan in animals. Methods of screening for compounds that modulate longevity by assaying wwp-1 ubiquitination pathway parameters are provided, as are related systems. In addition, methods of using wwp-1 and/or ubc-18 to modulate longevity or delay onset of age-related diseases are described.

Abstract: CHI like fatty acid binding proteins and genes, recombinant cells and organisms, methods of metabolic pathway engineering to improve lipid production in cells, Crystal structures of CHI like fatty acid binding proteins, methods of engineering CHI like fatty acid binding proteins and systems thereof are provided.

Abstract: Site-specific recombinases provide a means of efficiently manipulating chromosomal sequences in mammalian cells in culture and in mice. Embryonic stem cells containing recombinase nucleic acid constructs that were expressed in the male germline would simplify current protocols for producing mice bearing homologously recombined alleles that have been secondarily rearranged by a site-specific recombinase, five lines of transgenic mice containing a fusion gene consisting of the mouse protamine 1 gene promoter and the Cre recombinase coding sequence (ProCre nucleic acid constructs) showed high levels of Cre-mediated recombination of the germline, but did not show appreciable recombination in other tissues. In different ProCre strains, between 80% and 100% of the progeny that inherited a Cre target nucleic acid construct from males that were also heterozygous for a ProCre nucleic acid construct inherited the Cre-recombined target.

Abstract: This invention provides recombinant cells and transgenic plants that display selectively increased or decreased response to brassinosteroids, resulting in increased yield. Methods of modulating brassinosteroid responses, and of modulating plant phenotypes, are provided.

Abstract: Antitoxin and vaccine compositions based on nodavirus VLPs are provided. Anthrax antitoxin and vaccine compositions are provided. Methods of treating toxins with VLP-based antitoxins are provided. Methods of raising an immune response with immunogen decorated VLPs are provided.

Abstract: A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis.

Abstract: The invention provides crystalline O-methyltransferases and isolated non-native O-methyltransferases as well as sets of their structural coordinates. Also provided are methods of predicting the activity or substrate specificity of putative O-methyl-transferases, methods of identifying potential substrates of O-methyltransferases, and methods of identifying potential inhibitors of methyltransferases.

Abstract: SRIF peptide antagonists, which are selective for SSTR2 in contrast to the other cloned SRIF receptors and which bind with high affinity to the cloned human receptor SSTR2 but do not activate the receptor, have many useful functions. Because they do not bind with significant affinity to SSTR1, SSTR3, SSTR4 or SSTR5, their administration avoids potential undesirable side effects. Because they block the receptor function, they can be used therapeutically to block certain physiological effects which SSTR2 mediates. By incorporating radioiodine or the like in these SSTR2-selective SRIF antagonists, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, highly radioactive moieties can be N-terminally coupled, complexed or chelated thereto.

Abstract: The invention relates to transgenic plants having reduced sensitivity to ethylene as a result of having a recombinant nucleic acid encoding an F-box protein that interacts with a EIN3 involved in an ethylene response of plants, and a method of producing a transgenic plant with reduced ethylene sensitivity by transforming the plant with a nucleic acid sequence encoding an F-box protein. The inventions also relates to methods of altering the ethylene response in a plant by modulating the activity or expression of an F-box protein.

Abstract: Described herein are flavonoids (e.g., 5-desoxy flavones and/or 5-desoxy flavonols, including without limitation fisetin and its derivatives) that activate ERK and induce CREB phosphorylation in neuronal cultures, facilitate long-term potentiation in hippocampal slices and enhance object recognition in vivo. Methods of using these flavonoids, for instance, for enhancing memory are described.

Abstract: In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein: an extracellular, ligand-binding domain, a hydrophobic, trans-membrane domain, and an intracellular, receptor domain having serine kinase-like activity. The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-? superfamily of polypeptide growth factors such that concentrations of ?10 nM of said polypeptide growth factor occupy ?50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factor-?, and other non-activin-like proteins.

Abstract: CRF peptide analogs that bind to CRFR1 with an affinity far greater than they bind to CRFR2. Some of these analogs exhibit CRF agonist activity. One exemplary analog that may be made by solid-phase synthesis is: (cyclo 31-34)[Ac-Pro4,D-Phe12,Nle18,21,Glu31,Lys34]-sucker urotensin(4-41).

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek gene to modulate both longevity and stress tolerance, are described.

Abstract: This disclosure concerns compositions and methods for immunoenhancement and/or immunosuppression. In certain embodiments, the disclosure concerns methods of using a TAM receptor inhibitor for immunoenhancement, for example as a vaccine adjuvant, for the treatment of sepsis, or for treating an immunocompromised subject. Also disclosed are methods of screening for immunoenhancing agents. In other embodiments, the disclosure concerns methods of using a TAM receptor agonist for immunosuppression, for example as a treatment for an autoimmune disorder, for the treatment of an allergy, or for treating graft-versus-host disease in a subject. Also disclosed are methods of screening for immunosuppressive agents.