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Signaling output of bone morphogenetic proteins (BMPs) is determined by two sets of opposing interactions, one with heterotetrameric complexes of cell surface receptors, the other with secreted antagonists that act as ligand traps. We identified two mutations (N445K,T) in patients with multiple synostosis syndrome (SYM1) in the BMP-related ligand GDF5.(More)
Beta-D-glucosyl-ifosfamide mustard (D 19575, glc-IPM, INN = glufosfamide) is a new agent for cancer chemotherapy. Its mode of action, which is only partly understood, was investigated at the DNA level. In the breast carcinoma cell line MCF7 glufosfamide inhibited both the synthesis of DNA and protein in a dose-dependent manner, as shown by the decreased(More)
PURPOSE To investigate transcription of members of the transforming growth factor (TGF)-beta superfamily and corresponding receptors in human corneal epithelium and stroma. METHODS Transcription of bone morphogenetic proteins (BMP)-2, BMP-3, BMP-4, BMP-5, and BMP-7; growth- differentiation factor (GDF)-5), and BMP receptors (BMPR) types I (BMPR-IA,(More)
Growth/differentiation factor 5 (GDF5) is a novel member of the transforming growth factor-beta (TGF-beta) superfamily of multifunctional cytokines. We show here that GDF5 is expresed in the developing CNS including the mesencephalon and acts as a neurotrophic, survival promoting molecule for rat dopaminergic midbrain neurons, which degenerate in(More)
Expression of the dopaminergic neurotrophin GDF-5 in developing rat ventral mesencephalon (VM) was found to begin at embryonic day (E) 12 and peak on E14, when dopaminergic neurones undergo terminal differentiation. In the adult rat, GDF-5 was found to be restricted to heart and brain, being expressed in many areas of the brain, including striatum and(More)
Growth/differentiation factor 5 (GDF5) is a neurotrophin which protects the rat nigrostriatal dopaminergic pathway from 6-hydroxydopamine-induced damage. Here we used amphetamine-induced rotational testing, high-performance liquid chromatography and immunocytochemistry to investigate the minimum effective dose of GDF5. We also compared the effectiveness of(More)
  • Jens Pohl, Art Chapman, Kym Jason Pohl, Jonathan Primrose, Adam Wozniak
  • 2003
This report describes work performed by the Collaborative Agent Design Research Center (CADRC) over the past several years in the design and implementation of collaborative, computer-based, decision-support systems, mostly for military applications. In these systems multiple components, either program modules or separate processes (i.e., software agents),(More)
We investigated a family with a brachydactyly type A2 and identified a heterozygous arginine to glutamine (R380Q) substitution in the growth/differentiation factor 5 (GDF5) in all affected individuals. The observed mutation is located at the processing site of the protein, at which the GDF5 precursor is thought to be cleaved releasing the mature molecule(More)