ABSTRACT
The article briefly presents the history of the formation of the forensic medicine service in Crimea. Information on the main legislative acts that determined the activities of forensic experts and the service in general at different historical stages is provided. The data on the heads of the service and well-known experts - forensic doctors, organizers of forensic medical examination in Crimea are presented. In parallel, the history of the organization and development of the Department of Forensic Medicine is described, the role of its employees in organizing the work of the Crimean Bureau of Forensic Medical Expertise is presented. In this article, in addition to the available sources of literature and bibliography of legislative acts, materials from the archive of the Department of Forensic Medicine of Medical Academy named after S.I. Georgievsky of Vernadsky Crimean Federal University are used.
Subject(s)
Anniversaries and Special Events , Forensic Medicine , Forensic Medicine/education , Humans , UniversitiesABSTRACT
Fibroblast growth factors (FGFs) constitute a family of at least 23 structurally related heparin-binding proteins that are involved in regulation of cell growth, survival, differentiation and migration. Sucrose octasulfate (SOS), a chemical analogue of heparin, has been demonstrated to activate FGF signalling pathways. The structure of rat FGF1 crystallized in the presence of SOS has been determined at 2.2 A resolution. SOS-mediated dimerization of FGF1 was observed, which was further supported by gel-filtration experiments. The major contributors to the sulfate-binding sites in rat FGF1 are Lys113, Lys118, Arg122 and Lys128. An arginine at position 116 is a consensus residue in mammalian FGF molecules; however, it is a serine in rat FGF1. This difference may be important for SOS-mediated FGF1 dimerization in rat.
Subject(s)
Anti-Ulcer Agents/chemistry , Fibroblast Growth Factor 1/chemistry , Sucrose/analogs & derivatives , Animals , Binding Sites , Chromatography, Gel , Crystallography, X-Ray , DNA, Complementary , Dimerization , Escherichia coli/genetics , Fibroblast Growth Factor 1/chemical synthesis , Fibroblast Growth Factor 1/metabolism , Hydrogen Bonding , Models, Molecular , Molecular Weight , Protein Binding , Protein Structure, Tertiary , Rats , Sucrose/chemistry , Sucrose/metabolismABSTRACT
The cell adhesion molecules NCAM and L1 are considered to play key roles in neuronal development and plasticity. L1 has been shown to interact with NCAM, possibly through NCAM binding to oligomannosidic glycans present in L1. We investigated the effect of recombinant immunoglobulin (Ig) modules of NCAM involved in homophilic NCAM binding, on L1 induced neurite outgrowth from PC12-E2 cells and found a complete inhibition of L1 induced neurite outgrowth after addition of Ig-modules 1, 2 and 3 of NCAM, suggesting that the ligation state of NCAM is crucial for normal L1 signaling.
Subject(s)
Membrane Glycoproteins/metabolism , Neural Cell Adhesion Molecules/metabolism , Neurites/metabolism , Animals , Cell Aggregation/drug effects , Cell Division/drug effects , Coculture Techniques , Immunoglobulins/metabolism , Leukocyte L1 Antigen Complex , Mice , Neural Cell Adhesion Molecules/physiology , Protein Binding , Protein Conformation , Rats , Recombinant Proteins/metabolism , Transfection , Tumor Cells, CulturedABSTRACT
The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and learning. In this study, we identified a synthetic peptide-ligand of the NCAM Ig1 module by combinatorial chemistry and showed it could modulate NCAM-mediated cell adhesion and signal transduction with high potency. In cultures of dissociated neurons, this peptide, termed C3, stimulated neurite outgrowth by activating a signaling pathway identical to that activated by homophilic NCAM binding. A similar effect was shown for the NCAM Ig2 module, the endogenous ligand of NCAM Ig1. By nuclear magnetic resonance spectroscopy, the C3 binding site in the NCAM Ig1 module was mapped and shown to be different from the binding site of the NCAM Ig2 module. The C3 peptide may prove useful as a lead in development of therapies for neurodegenerative disorders, and the C3 binding site of NCAM Ig1 may represent a target for discovery of nonpeptide drugs.
Subject(s)
Cell Adhesion Molecules, Neuronal/metabolism , Combinatorial Chemistry Techniques , Neurites/metabolism , Peptide Library , Peptides/metabolism , Amino Acid Sequence , Consensus Sequence , Immunoglobulins/metabolism , Ligands , Magnetic Resonance Spectroscopy , Molecular Sequence Data , Signal Transduction , Surface Plasmon ResonanceABSTRACT
To study the function of the first immunoglobulin (Ig)-like domain of the neural cell adhesion molecule (NCAM), it was produced as a recombinant fusion protein in a bacterial expression system and as a recombinant protein in a eukaryotic expression system of the yeast Pichia pastoris. For comparison, other NCAM domains were also produced as fusion proteins. By means of surface plasmon resonance analysis, it was shown that the first Ig-like NCAM domain binds the second Ig-like NCAM domain with a dissociation constant 5.5 +/- 1.6 x 10(-5) M. Furthermore, it was found that the first Ig-like domain binds heparin. It was also demonstrated that the second Ig-like NCAM domain binds heparin and that both domains bind collagen type I via heparin but not collagen type I directly.
Subject(s)
Heparin/metabolism , Immunoglobulins/chemistry , Neural Cell Adhesion Molecules/chemistry , Animals , Binding Sites , Cell Aggregation/drug effects , Cerebellum/cytology , Electrophoresis, Polyacrylamide Gel , Exons , Mice , Models, Molecular , Neural Cell Adhesion Molecules/metabolism , Neurons/cytology , Protein Conformation , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolismABSTRACT
In order to characterize the functions of the two fibronectin type III (F3) homology domains of the neural cell adhesion molecule (NCAM), we investigated the effects of two variants, expressed as fusion proteins, of the NCAM-F3 domains on attachment and spreading of NCAM-expressing fibroblasts, cerebellar cell aggregation and fiber formation, and on growth cones. The two fusion proteins were different with regard to a short proline-rich insert of six amino acids between the two F3 domains. Immobilized NCAM-F3 fusion proteins were found to mediate attachment of both transmembrane and lipid-anchored NCAM expressing fibroblasts. Also NCAM-negative cells adhered to the NCAM-F3 substratum, although to a lesser extent, implying the possibility of a heterophilic ligand to NCAM-F3 domains on the surface of fibroblasts. Cellular spreading on NCAM-F3 substratum was selectively increased in fibroblasts expressing transmembrane NCAM, and only the NCAM-F3 fusion protein lacking the proline-rich insert was able to elicit this effect. Primary cultures of mouse cerebellum were strongly inhibited with regard to formation of cellular aggregates and fibers, when incubated in the presence of either of the two NCAM-F3 fusion proteins, the fusion protein with the proline-rich insert being the more effective one. Finally, the morphology of growth cones from rat cerebellar granule cells changed significantly when grown on NCAM-F3 substrata as revealed by computer-assisted image analysis. Thus, our data indicate that the NCAM-F3 domain are involved in cell-cell adhesion, and that insertion of the proline-rich sequence has a modulatory effect on NCAM-F3 domain functions.
