Abstract:
The present disclosure provides attractin/mahogany-like polypeptides and fragments thereof, polynucleotides encoding such polypeptides and fragments, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides or fragments, and assays and methods employing these polypeptides, antibodies, and polynucleotides.
Abstract:
The present invention is directed to methods for the identification and uses of receptors that interact with anti-inflammatory compounds derived from eicosapentaenoic acid (EPA). The receptors are of the G-protein coupled receptor (GPCR) family, and are useful to screen candidate substances for anti-inflammatory activity, especially substances that are analogs of EPA. Such analogs are termed “resolvins”; and are typically di- and tri-hydroxy EPA analogs. One analog herein denoted Resolvin E1 was identified in humans and prepared by total synthesis. In nanomolar range Resolvin E1 reduces dermal inflammation, peritonitis, dendritic cells (DCs) migration and IL-12 production. Also described herein is a receptor denoted Reso ER1 that interacts with Resolvin E1 to attenuate cytokine induced activation of inflammatory pathways mediated by transcription factor (NF)-kB. Treatment of DCs with small-interfering RNA specific for ResoE1 eliminated the ligand's ability to regulate IL-12. Assays of anti-inflammatory activity based on these discoveries are also described.
Abstract:
The present invention relates to a multicellular model comprising at least, as cell type: keratinocytes, melanocytes, and nerve cells, in which the keratinocytes and the melanocytes form a first cell layer, said nerve cells form a second cell layer devoid of physical contact with the first cell layer, said first and second cell layers being arranged so as to be compatible with a manifestation of at least one cellular chemical exchange.
Abstract:
This application is directed to a process of identifying a compound capable of modulating activity of a human ENDO180 receptor that comprises the steps of measuring the binding of the ENDO180 receptor to an interactor with which the ENDO180 receptor interacts specifically in vivo, in the absence or presence of a compound, and determining whether the binding of the ENDO180 receptor to the interactor is affected by the compound. This application is also directed to use of a compound identified by that process in the preparation of a medicament for therapy of disease, in particular fibrosis. This application also relates to the use of ENDO180 modulators in treatment of disease.
Abstract:
The present invention is directed to methods for detecting or measuring Notch activation by observing or measuring the appearance of Notch on the cell surface or by observing or measuring Notch cleavage products that are indicative of Notch activation. The present invention is also directed to methods for detecting a molecule that modulates Notch activation by observing or measuring a change in the amount of Notch expressed on the cell surface or a change in the amount or pattern of Notch cleavage products. The present invention is also directed to a substantially purified activated heterodimeric form of Notch and components thereof and pharmaceutical compositions and kits thereof. The present invention is based, at least in part, on the discovery that Notch in its active form, i.e., the form that mediates signal transduction and that binds Notch ligands such as Delta, is a heterodimer of an about 180 kDa subunit (NEC) and an about 110 kDa subunit (NTM), which are tethered together through a reducing agent-sensitive linkage, in particular, a non-covalent, metal ion-dependent linkage.
Abstract:
Celiac Sprue and/or dermatitis herpetiformis are treated by interfering with HLA binding of immunogenic gluten peptides. The antigenicity of gluten oligopeptides and the ill effects caused by an immune response thereto are decreased by administration of an HLA-binding peptide inhibitor. Such inhibitors are analogs of immunogenic gluten peptides and (i) retain the ability to bind tightly to HLA molecules; (ii) retain the proteolytic stability of these peptides; but (iii) are unable to activate disease-specific T cells.
Abstract:
The present invention provides cell-based screening assays designed to identify agents that regulate the activity of the polycystic kidney disease proteins encoded by the PKD-1 and PKD-2 genes and that may be useful in the treatment of polycystic kidney disease. The assays of the invention comprise the contacting of genetically engineered cells expressing a mutant or truncated PKD gene product with a test agent and assaying for a decrease in the PKD mediated mutant phenotype. Characteristics associated with such a mutant phenotype include increased adherence to type I collagen coated surfaces; apical expression of NaK-ATPase on the cell membrane; increased expression of &bgr;-2-NaK-ATPase; and decreased focal adhesion kinase (FAK) incorporation into focal adhesion complexes, and inability to form tubular structures in a gel matrix. To facilitate the screening methods of the invention, cells may be genetically engineered to express epitope tagged PKD gene products and/or epitope tagged PKD interacting proteins (PKD-IP). Such interacting proteins include, for example, focal adhesion complex proteins such as FAK, paxillin, vinculin, talin and the like.
Abstract:
The disclosure provides for multilayered organ-on-a-chip systems that can be used to generate topographic neural organoids, and uses thereof, including as models to study neurological disorders.
Abstract:
Methods and systems are provided for sample preparation techniques and sequencing of macromolecular constituents of cells and other biological materials.