Abstract: The invention provides isolated nucleic acid molecules encoding PAAD-domain containing polypeptides and functional fragments thereof, including fragments containing PAAD domains, NACHT domains and ARED domains, encoded polypeptides, and antibodies. Also provided are methods of identifying polypeptides and agents that associate with a PAAD-domain containing polypeptide or fragment thereof, or that alter an association of a PAAD domain-containing polypeptides. Further provided are methods of identifying agents that modulate PAAD domain-mediated inhibition of NFKB activity, or modulate an activity of a NACHT domain of a PAAD domain-containing polypeptide. Also provided are methods of modulating NFKB transcriptional activity in a cell, and methods of altering expression of a PAAD domain-containing polypeptide in a cell.

Abstract: The present invention provides a conjugate containing a moiety linked to a homing molecule that selectively homes to tumor lymphatic vasculature. The invention also provides a method of directing a moiety to tumor lymphatic vasculature in a subject by administering to the subject a conjugate containing a moiety linked to a homing molecule that selectively homes to tumor lymphatic vasculature.

Abstract: We have developed a reduced Drosophila heart preparation in which dissection of the fly heart removes nervous system input and reveals its inherent myogenic activity, which can be preserved for several hours. High speed image capture combined with computer-based analytical packages allows us to generate the equivalent of M-mode traces obtained from ultrasounds of human hearts.

Abstract: The present invention provides a method of directing a moiety to breast vasculature in a subject by administering to the subject a conjugate which contains a moiety linked to a homing molecule that selectively homes to breast vasculature, whereby the moiety is directed to breast vasculature. In one embodiment, the homing molecule is a peptide containing the amino acid sequence PGPEGAG (SEQ ID NO: 1), or a peptidomimetic thereof.

Abstract: In accordance with the present invention, there are provided novel TRAF-Protein-Binding-Domain polypeptides (TPBDs). The invention also provides nucleic acid molecules encoding TPBDs, vectors containing these nucleic acid molecules and host cells containing the vectors. The invention also provides antibodies that can specifically bind to invention TPBDs. Such TPBDs and/or anti-TPBD antibodies are useful for discovery of drugs that suppress autoimmunity, inflammation, allergy, allograph rejection, sepsis, and other diseases.

Abstract: The present disclosure provides compounds having the general structure A or pharmaceutically acceptable salts thereof: R—X??(A) wherein R is an alkyl or aryl moiety comprising heterocyclic structures; and X is a metal-chelatin group selected from: This disclosure further provides a focused library of compounds for use in the discovery and design of metallo-enzyme inhibitors. This fragment-based approach provides an assembly of a library of low molecular weight compounds (MW<300 Da) containing a variety of potential metal-chelating groups. The identification of the inhibitory scaffolds among these compounds provides the initial hit fragments that may be optimized for affinity against a particular target using common medicinal chemistry, structure-based or NMR-based approaches.

Abstract: This disclosure generally relates to components and methods of using a high throughput screening (HTS) systems for intracellular proteases, using Caspases as a prototype. Genetic systems are disclosed for monitoring exogenous caspase activation pathways in the yeast, Saccharomyces cerevisiae. The yeast-based cellular systems permit facile expression of proteases (e.g., caspase) and protease-activating proteins in combinations that reconstitute entire mammalian pathways in these simple eukaryotes. Among the assay methods integrated into the yeast system are cleavable reporter gene activators, in which protease-mediated cleavage activates a transcription factor. Exemplary systems rely, singly or in concert, on exogenous recombinant caspases and exogenous upstream activators of caspases to cleave a chimeric protein giving rise to a transcription factor which induces the expression of the LacZ and LEU2 genes.

Abstract: Novel methods of regulating cellular apoptosis by affecting the interaction of hepatitis B X-interacting protein (HBXIP) with Survivin are described. More specifically, these novel methods of enhancing apoptosis of neoplastic cells comprises inhibiting interaction of hepatitis B X-interacting protein (HBXIP) with Survivin using siRNA or antisense compounds.

Abstract: Disclosed are modulators, i.e., activators and inhibitors, of Intestinal Alkaline Phosphatase (IAP). Also disclosed are methods for treating bacterial infections of the intestinal tract and methods for maintaining the health of the intestinal tract using IAP activators. Further disclosed are methods to assist in weight gain of emaciated patients and those having reduced or negligible fat absorption using IAP inhibitors.

Abstract: The invention provides compounds that can efficiently and specifically inhibit bacterial toxins, such as inhibit the lethal factor (LF) protease activity of anthrax toxin and/or botulinum neurotoxin type A. The invention also provides methods for inhibiting proteases, such as lethal factor protease, as well as methods for treating bacterial infections, such as anthrax and botulinum.

Abstract: The invention provides Bcl-G polypeptides and encoding nucleic acids. Bcl-G polypeptides include Bcl-GL and Bcl-GS. The invention also provides mouse Bcl-G. The invention also provides vectors containing Bcl-G nucleic acids, host cells containing such vectors, Bcl-G anti-sense nucleic acids and related compositions. The invention additionally provides Bcl-G oligonucleotides that can be used to hybridize to or amplify a Bcl-G nucleic acid. Anti-Bcl-G specific antibodies are also provided. Further provided are kits containing Bcl-G nucleic acids or Bcl-G specific antibodies. Such kits and reagents can be used to diagnose cancer, monitor response to therapy, or predict the prognosis of a cancer patient. The invention additionally provides methods of modulating apoptosis using Bcl-G polypeptides, encoding nucleic acids, or compounds that modulate the activity or expression of Bcl-G polypeptides. The methods for modulating apoptosis can be used to treat diseases such as cancer.

Abstract: The present invention provides tumor homing molecules, which selectively home to a tumor. The invention also provides methods of using a tumor homing molecule to target an agent such as a drug to a selected tumor or to identify the target molecule expressed by the tumor. The invention also provides methods of targeting a tumor containing angiogenic vasculature by contacting the tumor with a molecule that specifically binds an ?v-containing integrin. The invention further provides molecules that can selectively home to angiogenic vasculature. In addition, the invention provides a target molecule, which is specifically bound by a tumor homing molecule and is expressed by angiogenic vasculature. The invention also provides antibodies that bind to the target molecule and peptidomimetics that competitively inhibit binding of a ligand to the target molecule.

Abstract: The present invention provides tumor homing molecules, which selectively home to a tumor. The invention also provides methods of using a tumor homing molecule to target an agent such as a drug to a selected tumor or to identify the target molecule expressed by the tumor. The invention also provides methods of targeting a tumor containing angiogenic vasculature by contacting the tumor with a molecule that specifically binds an ?v-containing integrin. The invention further provides molecules that can selectively home to angiogenic vasculature. In addition, the invention provides a target molecule, which is specifically bound by a tumor homing molecule and is expressed by angiogenic vasculature. The invention also provides antibodies that bind to the target molecule and peptidomimetics that competitively inhibit binding of a ligand to the target molecule.

Abstract: The invention provides caspase recruitment domain (CARD)-containing polypeptides, CARD, NB-ARC, ANGIO-R, LRR and SAM domains therefrom, as well as encoding nucleic acid molecules and specific antibodies. The invention also provides related screening, diagnostic and therapeutic methods.

Abstract: The present invention provides a family of BAG-1 related proteins from humans (BAG-1L, BAG-1, BAG-2, BAG-3, BAG-4 and BAG-5), the invertebrate C. elegans (BAG-1, BAG-2) and the fission yeast S. pombe (BAG-1A, BAG-1B) and the nucleic acid molecules that encode them.

Abstract: Provided herein are compositions and methods of detecting Bcl-B expression in cancer cells to prognose, monitor, or select therapies for cancers such as breast cancer, prostate cancer, lung cancer, or gastric cancer.

Abstract: Disclosed herein are compositions and methods for assaying ubiquitination independent of ubiquitin ligase (E3) or a target protein.

Abstract: A compound having the structure A is described as well as the use of such compounds to inhibit at least one BCL-2 protein family member.

Abstract: The present invention provides a method of identifying a tumor homing molecule that homes to angiogenic vasculature by contacting a substantially purified NGR receptor with one or more molecules and determining specific binding of a molecule to the NGR receptor, where the presence of specific binding identifies the molecule as a tumor homing molecule that homes to angiogenic vasculature. The invention also provides a method of directing a moiety to angiogenic vasculature in a subject by administering to the subject a conjugate including a moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor, whereby the moiety is directed to angiogenic vasculature. In addition, the invention provides a method of imaging the angiogenic vasculature of a tumor in a subject by administering to the subject a conjugate having a detectable moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor and detecting the conjugate.

Abstract: The invention provides isolated MMP-2, MMP-9 and MT1-MMP selective substrate polypeptides or functional peptidomimetics. The selective substrate polypeptides contain the following sequences: MMP-2 selective substrate polypeptides contain SEQ ID NOS:1-27, MMP-9 selective substrate polypeptides contain SEQ ID NOS:28-35, and MT1-MMP selective substrate polypeptide contain SEQ ID NOS:36-40. In addition, the invention provides a method of preferentially directing a moiety to a site of MMP-2 activity by administering to a subject an effective amount of an isolated MMP-2 selective substrate polypeptide containing SEQ ID NOS:45-47 linked to a moiety.