Comparative investigations of structure and properties of micro-arc wollastonite-calcium phosphate coatings on titanium and zirconium-niobium alloy

Investigation results of micro-arc wollastonite–calcium phosphate (W–CaP) biocoatings on the pure titanium (Ti) and Zr–1wt.%Nb (Zr–1Nb) alloy were presented. The voltages of 150–300 V generate the micro-arc oxidation (MAO) process with the initial amplitude current of 150–550 A and 100–350 A for Ti and Zr–1Nb substrates, respectively. The identical dependencies of changes of the coating thickness, surface roughness and adhesion strength on the process voltage were revealed for the both substrates. The W–CaP coatings with the thickness of 10–11 μm were formed on Ti and Zr–1Nb under the low process voltage of 130–150 V. Elongated wollastonite particles with the size in the range of 40–100 μm were observed in such coatings. The structure of the coatings on Ti was presented by the X–ray amorphous and crystalline phases. The X–ray reflexes relating to the crystalline phases of Ti and wollastonite were observed only in XRD patterns of the coatings deposited under 130–200 V on Ti. While, the crystalline structure with phases of CaZr4(PO4)6, β–ZrP2O7, ZrO2, and Zr was detected in the coatings on Zr–1Nb. FT–IRS, XRD, SEM, and TEM data confirmed that the increase of the process voltage to 300 V leads to the dissociation of the wollastonite. No toxic effect of specimens on a viability, morphology and motility of human adipose–derived multipotent mesenchymal stem cells was revealed in vitro

The investigation of structure–activity relationship of polyamine-targeted synthetic compounds from different chemical groups

The polyamine (PA) metabolism is involved in cell proliferation and differentiation. Increased cellular PA levels are observed in different types of cancers. Products of PA oxidation induce apoptosis in cancer cells. These observations open a perspective to exploit the enzymes of PA catabolism as a target for anticancer drug design. The substances capable to enhance PA oxidation may become potential anticancer agents. The goal of our study was to explore how the mode of ligand binding with a PA catabolic enzyme is associated with its stimulatory or inhibitory effect upon PA oxidation. Murine N1-acetylpolyamine oxidase (5LFO) crystalline structure was used for molecular docking with ligands of various chemical structures. In vitro experiments were carried out to evaluate the action of the tested compounds upon PA oxidative deamination in a cell-free test system from rat liver. Two amino acid residues (Aps211 and Tyr204) in the structure of 5LFO were found to be significant for binding with the tested compounds. 19 out of 51 screened compounds were activators and 17 were inhibitors of oxidative deamination of PA. Taken together, these results enabled to construct a recognition model with characteristic descriptors depicting activators and inhibitors. The general tendency indicated that a strong interaction with Asp211 or Tyr204 was rather typical for activators. The understanding of how the structure determines the binding mode of compounds with PA catabolic enzyme may help in explanation of their structure–activity relationship and thus promote structure-based drug design. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature

Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors

Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling between apoptotic and surviving cancer cells remain elusive. In this study, we demonstrate that apoptotic GBM cells paradoxically promote proliferation and therapy resistance of surviving tumor cells by secreting apoptotic extracellular vesicles (apoEVs) enriched with various components of spliceosomes. apoEVs alter RNA splicing in recipient cells, thereby promoting their therapy resistance and aggressive migratory phenotype. Mechanistically, we identified RBM11 as a representative splicing factor that is upregulated in tumors after therapy and shed in extracellular vesicles upon induction of apoptosis. Once internalized in recipient cells, exogenous RBM11 switches splicing of MDM4 and Cyclin D1 toward the expression of more oncogenic isoforms. © 2018 Elsevier Inc.Pavlyukov et al. show that apoptotic GBM cells secrete vesicles enriched with components of spliceosomes to alter RNA splicing in surviving tumor cells and promote their aggressiveness. They identify RBM11 as one such factor that switches MDM4 and cyclinD1 toward the more oncogenic isoforms in recipient cells

Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors

Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling between apoptotic and surviving cancer cells remain elusive. In this study, we demonstrate that apoptotic GBM cells paradoxically promote proliferation and therapy resistance of surviving tumor cells by secreting apoptotic extracellular vesicles (apoEVs) enriched with various components of spliceosomes. apoEVs alter RNA splicing in recipient cells, thereby promoting their therapy resistance and aggressive migratory phenotype. Mechanistically, we identified RBM11 as a representative splicing factor that is upregulated in tumors after therapy and shed in extracellular vesicles upon induction of apoptosis. Once internalized in recipient cells, exogenous RBM11 switches splicing of MDM4 and Cyclin D1 toward the expression of more oncogenic isoforms. © 2018 Elsevier Inc.Pavlyukov et al. show that apoptotic GBM cells secrete vesicles enriched with components of spliceosomes to alter RNA splicing in surviving tumor cells and promote their aggressiveness. They identify RBM11 as one such factor that switches MDM4 and cyclinD1 toward the more oncogenic isoforms in recipient cells

Language structure: psychological and social constraints

Jäger G, van Rooij R. Language structure: psychological and social constraints. Synthese. 2007;159(1):99-130.In this article we discuss the notion of a linguistic universal, and possible sources of such invariant properties of natural languages. In the first part, we explore the conceptual issues that arise. In the second part of the paper, we focus on the explanatory potential of horizontal evolution. We particularly focus on two case studies, concerning Zipf's Law and universal properties of color terms, respectively. We show how computer simulations can be employed to study the large scale, emergent, consequences of psychologically and psychologically motivated assumptions about the working of horizontal language transmission