Abstract: We have identified ZNF206, a novel repressor of human embryonic stem cell (hESC) differentiation. Repressing extra-embryonic endoderm development preserves the pluripotent state of human embryonic stem cells, and, conversely downregulating expression of ZNF206 in hESCs causes them to upregulate the expression of genes associated with the extra-embryonic endodermal lineage, down-regulate genes associated with the pluripotent state, and may lead to the further emergence of genes associated with even more differentiated lineages and phenotypes.

Abstract: This invention relates to Applicant's discovery that Metabolic Syndrome, a cluster of disorders stemming from a resistance to insulin, contributes directly to dementia, particularly Alzheimer's disease. Applicant's invention includes a screening method to determine susceptibility and diagnosis of dementia based on the risk factors for Metabolic Syndrome. Applicant's invention further includes methods for the prevention or treatment of dementia and other neurological conditions based on (1) minimizing insulin resistance, thereby preventing excess biosynthesis of insulin; (2) modulating the activity of IDE such that insulin competes less efficiently with ?-amyloid protein for the IDE; and (3) blocking the consequences of NMDA receptor activation, such as by minimizing the generation of NO and other harmful free radicals.

Abstract: Compositions and methods are provided that are based on a discovery that a combination of three compounds, doxycycline, selenium, and zinc, retards physiological age-related changes (for example cardiac aging and the decline in exercise capacity) and can also prolong survival.

Abstract: In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPs) and/or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and/or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and/or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and/or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein. Also provided are compositions and methods for targeting the destruction of selected polypeptides in eukaryotic cells based on the ubiquitin-independent mechanism by which ornithine decarboxylase is degraded by the 26S proteasome.

Abstract: The present invention provides a variety of isolated peptides and peptidomimetics, which can be useful, for example, in constructing the conjugates of the invention or, where the peptide itself has biological activity, in unconjugated form as a therapeutic for treating any of a variety of cardiovascular diseases as described below. Thus, the present invention provides an isolated peptide or peptidomimetic which has a length of less than 60 residues and includes the amino acid sequence CRPPR (SEQ ID NO: 1) or a peptidomimetic thereof. The invention further provides an isolated peptide or peptidomimetic which has a length of less than 60 residues and includes the amino acid sequence CARPAR (SEQ ID NO: 5) or a peptidomimetic thereof, or amino acid sequence CPKRPR (SEQ ID NO: 6) or a peptidomimetic thereof.

Abstract: Disclosed herein are tissue-nonspecific alkaline phosphatase (TNAP) activators and uses thereof for promoting bone mineral deposition.

Abstract: There are provided methods of inhibiting growth and metastasis of melanoma, methods of sensitizing melanoma cells to apoptosis, and methods of treating a subject having melanoma using acetyl isogambogic acid, celastrol, or a derivative thereof. There are further provided derivatives of celastrol and compositions comprising acetyl isogambogic acid, celastrol, or a derivative thereof.

Abstract: Neurite outgrowth-promoting prostaglandins (NEPPs) and other electrophilic compounds bind to Keap1, a negative regulator of the transcription factor Nrf2, and prevent Keap1-mediated inactivation of Nrf2 and, thus, enhance Nrf2 translocation into the nucleus of neuronal cells. Therefore, neuroprotective compositions and related methods are provided that employ such neuroprotective compounds, and prodrugs of such compounds, to cause dissociation of Nrf2 from a Keap1/Nrf2 complex.

Abstract: The present invention provides a conjugate containing a therapeutic agent linked to a homing molecule that selectively homes to tumor vasculature and selectively binds collagen such as non-helical collagen or collagen IV. In one embodiment, the conjugate contains a homing peptide or peptidomimetic that includes the amino acid sequence CREKA (SEQ ID NO: 1) or a conservative variant or peptidomimetic thereof.

Abstract: The present invention relates to methods of identifying antagonists of GPR22, a G protein-coupled receptor (GPCR) and related compositions and methods. Antagonists of GPR22 are useful as therapeutic agents for the treatment of ischemic heart disease, including myocardial infarction, post-myocardial infarction remodeling, and congestive heart failure.

Abstract: We have identified a new variant of ileal bile acid binding protein (IBABP), designated IBABP-L, which is a biomarker for colorectal cancer. The transcript for IBABP-L arises from an alternative start site and includes three exons that are absent in IBABP. IBABP-L also shares part of a fourth exon with IBABP. The protein encoded by IBABP-L contains a deduced 49 residue N-terminal sequence that is not found in the IBABP protein. The present invention provides methods for diagnosing colorectal cancer and other compositions and methods based on this discovery.

Abstract: In accordance with the present invention, there are provided peptides that bind to a member of the mammalian selectin family and inhibit the binding of a carbohydrate to the selectin. Invention peptides are useful to inhibit of the adhesion of cells containing particular cell-surface carbohydrates to cells containing cell-surface selectins. Also provided are pharmaceutical compositions comprising invention peptides useful in methods for inhibiting a carbohydrate from binding to a selectin, and in methods of inhibiting tumor cell metastasis in a subject.

Abstract: The present invention provides compounds having the general structure I, or a pharmaceutically acceptable salt thereof: wherein Z is selected from a group consisting of O, C, N, and S; each of Ar1, Ar2, and Ar3 is a moiety selected from a group consisting of an aryl and a substituted aryl; Y is selected from a group consisting of S, O, CH2 and SO2; K is selected from a group consisting CH2, CF2, O, NH, and SO2; each of n1 and n2 is an integer selected from a group consisting of 0, 1, 2, 3, and 4; and each of x, y, m1 and m2 is an integer selected from a group consisting of 0 and 1. Pharmaceutical compositions based on compounds I are also provided for treatment of a neurological disorders, diseases, or pathologies, and for treatment of infectious diseases.

Abstract: Methods for screening for inhibitors of endoplasmic reticulum (ER) stress are provided. These methods involve the addition of thapsigargin, which induces ER stress, and a test agent to mammalian cells in multi-well plates. Cell survival can be readily monitored by measuring intracellular ATP content using a bioluminescent reagent. Screening a commercially available library of 50,000 compounds led to the identification of 93 hit compounds that were subjected to secondary assays to confirm their ability to rescue cells from thapsigargin-induced cell death.

Abstract: The present invention provides a method of providing acute neuroprotection by inducing the erythropoietin (EPO) signaling pathway in neuronal cells close to or subsequent to the time of excitatory insult; and inducing an insulin-like growth factor (IGF) signaling pathway in the neuronal cells close to or subsequent to the time of excitatory insult, thereby producing a synergistic acute neuroprotective effect in the neuronal cells. The invention also provides a method of preventing or reducing the severity of a neurologic condition in a subject by administering to the subject EPO or an active fragment or analog thereof at a dose of at most 2000 U/kg; and administering to the subject an IGF or an active fragment or analog thereof, thereby providing neuroprotection and preventing or reducing the severity of the neurologic condition.

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.

Abstract: This invention provides pure populations of neural precursor cells, capable of differentiation into neurons, glial cells, and astrocytes. The populations are obtained by culturing stem cell populations (such as embryonic stem cells) in a cocktail of growth conditions that initiates differentiation, and establishes the neural precursor population. The precursors can be further differentiated in culture into a variety of different neural phenotypes. The neural precursors can be generated in pure form (at least 99%) and in large quantities for use in drug screening and the treatment of neurological disorders.

Abstract: Stem cells, including mammalian, and particularly primate primordial stem cells (pPSCs) such as human embryonic stem cells (hESCs), hold great promise for restoring cell, tissue, and organ function. However, cultivation of stem cells, particularly undifferentiated hESCs, in serum-free, feeder-free, and conditioned-medium-free conditions remains crucial for large-scale, uniform production of pluripotent cells for cell-based therapies, as well as for controlling conditions for efficiently directing their lineage-specific differentiation. This instant invention is based on the discovery of the formulation of minimal essential components necessary for maintaining the long-term growth of pPSCs, particularly undifferentiated hESCs. Basic fibroblast growth factor (bFGF), insulin, ascorbic acid, and laminin were identified to be both sufficient and necessary for maintaining hESCs in a healthy self-renewing undifferentiated state capable of both prolonged propagation and then directed differentiation.

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.

Abstract: The present invention relates to a bladder tumor-targeting peptide and use thereof. More particularly, the present invention relates to a bladder tumor-targeting peptide having an amino acid sequence represented by SEQ ID NO: 7 and use thereof. The peptide according to the present invention is capable of specific binding to bladder tumor cells in vivo and in vitro. The peptide according to the present invention or an antibody thereof is useful for a marker for the diagnosis of bladder tumors, and for a drug carrier targeting bladder tumor.