Irina Makarova

M(m)H(n)(XO4)((m+n)/2) crystals: structure, phase transitions, hydrogen bonds, conductivity. I. K9H7(SO4)8·H2O crystals--a new representative of the family of solid acid conductors.

To reveal the structural conditionality for anomalies in physical properties, including dielectric and optical properties, diffraction studies of K9H7(SO4)8·H2O crystals were performed using synchrotron radiation in the temperature range 293-450 K and determined at 405 K, taking H atoms into account. The results indicate that the occurrence of high conductivity in K9H7(SO4)8·H2O crystals with a temperature increase is associated with the outward diffusion of water molecules, hydrogen-bond network rearrangement and the formation of channels for the possible motion of K(+) ions. A rearranged system of hydrogen bonds consists of permanent bonds and partly of dynamically disordered bonds. Hydrogen-bond rearrangement and the hindered back diffusion of water to the crystal bulk stabilize the high-temperature crystal structure right down to room temperature.

MmHn(XO4)(m + n)/2 crystals: structure, phase transitions, hydrogen bonds, conductivity. II. Structure and properties of Cs3(HSO4)2(H2PO4) and Cs4(HSO4)3(H2PO4) single crystals

Cs3(HSO4)2(H2PO4) and Cs4(HSO4)3(H2PO4) single crystals were obtained for the first time based on a systematic study of the phase diagram of the CsHSO4-CsH2PO4-H2O ternary system. To reveal the structural conditionality for anomalies in physical properties, including dielectric and optical properties, diffraction studies of the crystal structure of Cs3(HSO4)2(H2PO4) and Cs4(HSO4)3(H2PO4) were performed, and their common structural features and differences were analyzed.

Effect of Mn(II) on error-prone DNA polymerase iota activity in extracts from human normal and tumor cells

DNA polymerase iota (Pol ι) which has some peculiar features and is characterized by an extremely error prone DNA synthesis, belongs to the group of enzymes preferentially activated by Mn2+ instead of Mg2+. In this work, using misGvA method (misincorporation of “G” versus “A”, method of Gening) we studied the effect of Mn2+ on DNA synthesis in cell extracts from a—normal human and murine tissues, b—human tumor (uveal melanoma), and c—cultured human tumor cell lines SKOV-3 and HL-60. Each group displayed characteristic features of Mn-dependent DNA synthesis. Changes in Mn-dependent DNA synthesis caused by malignant transformation of normal tissues are described. It was also shown that the error prone DNA synthesis catalyzed by Pol ι in extracts of all cell types was efficiently suppressed by an RNA aptamer (IKL5) against Pol ι obtained by us earlier. The results obtained suggest that IKL5 might be used to suppress enhanced activity of Pol ι in tumor cells.

Transient expression and activity of human DNA polymerase iota in loach embryos

Human DNA polymerase iota (Pol ι) is a Y-family DNA polymerase with unusual biochemical properties and not fully understood functions. Pol ι preferentially incorporates dGTP opposite template thymine. This property can be used to monitor Pol ι activity in the presence of other DNA polymerases, e.g. in cell extracts of tissues and tumors. We have now confirmed the specificity and sensitivity of the method of Pol ι activity detection in cell extracts using an animal model of loach Misgurnus fossilis embryos transiently expressing human Pol ι. The overexpression of Pol ι was shown to be accompanied by an increase in abnormalities in development and the frequency of pycnotic nuclei in fish embryos. Further analysis of fish embryos with constitutive or regulated Pol ι expression may provide insights into Pol ι functions in vertebrate animals.

Activity of error-prone DNA polymerase iota in different periods of house mouse Mus musculus ontogeny

Analysis of incorrect activity of error-prone DNA polymerase iota in M. musculus ontogeny demonstrated considerable changes in its activity, which peaks in most organs during prenatal development and decreases in the adult body. We propose that the capacity of error-prone DNA polymerases to synthesize on damaged DNA regions is critical for the realization of rapidly changing genetic program in mammalian embryogenesis, which relieves the replication block and prevents cell death.

Structure and properties of new crystals in CsHSO4 – CsH2PO4 – H2O system

ABSTRACT The phase diagram of the CsHSO4–CsH2PO4–H2O ternary system was systematically studied, from which it became possible to synthesize and grow new compounds of mixed sulfate-phosphates of cesium. Based on experimental data, their common structural features and differences, and structural conditionality for anomalies in physical properties were analyzed.

Alterations in Synthesis and Repair of DNA during the Development of Loach Misgurnus fossilis

Using a modified radiolabeled primer extension method (we named this modification misGvA—“misincorporation of G versus A”) we have investigated the DNA synthesis and repair at early and late stages of development of loach Misgurnus fossilis. The misincorporation activity of DNA polymerase iota (Pol ι) in wild-type loach could not be detected by this method at any stage of loach development. In transgenic loach overexpressing human Pol ι we have shown that the bypassing of DNA synthesis arrest after incorporation of mismatched nucleotide by Pol ι (the T-stop) was not associated with this enzyme. Non-transgenic loach larvae are virtually lacking the capacity for error correction of DNA duplex containing a mismatched nucleotide. Such repair activity develops only in the adult fish. It appears that the initial stages of development are characterized by more intensive DNA synthesis, while in terminal stages the repair activities become more prominent. The misGvA approach clearly indicates substantial changes in the DNA synthesis intensity, although the role of particular replicative and repair DNA polymerases in this process requires further study.

Expression of the human TRIM14 and its mutant form (P207L) promotes apoptosis in transgenic loaches

The tripartite-motif (TRIM)14 protein, one of the TRIM family members, was shown to participate in the antiviral and antibacterial defence. Besides, it appears to play an essential role in the processes of oncogenesis. In some types of human tumour cells, TRIM14 has been shown to inhibit apoptosis, while in others—the overexpression of TRIM14 promotes apoptosis. However, whether TRIM14 mediates apoptosis in the normal cells remains unknown. In the present study, we investigated the possible participation of the human TRIM14 gene and its mutant form (620C > T) in the induction of apoptosis in the transgenic larvae loach Misgurnus fossilis L. We observed that the expression of both forms of TRIM14 gene was accompanied by the increase of the frequency of pyknotic nuclei in fish embryos compared to control groups. Accordingly, using the TUNEL assay, the enhanced apoptosis was revealed upon expression of both forms of TRIM14 gene. The transcription of proapoptotic genes (bax, tp53, and casp9) was significantly increased in transgenic loaches expressing human wild-type TRIM14, but remained unchanged upon expression of its mutant form. In addition, the transcription of c-myc was upregulated in transgenic loaches expressing both forms. Thus, it can be assumed that during embryonic development TRIM14 has a proapoptotic effect on the cells via the activation of c-myc, tp53, and bax genes. Apparently, the mutant TRIM14 directs apoptosis via c-myc by p53-independent mechanism.

The nature of high conductivity in solid acid proton conductors

Increasing energy consumption rates stimulate global interest in the study and development of alternative energy sources. One of the most rapidly developing fields associated with alternative energy sources is hydrogen energetics. To directly produce electrical energy, special devices, i.e., fuel cells providing direct chemical to electrical energy conversion were developed. Interest in superprotonic crystals MmHn(AO4)m+n/2·yН2О (M = K, Rb, Cs, NH4; AO4 = SO4, SeO4, HPO4, HAsO4) is associated with the determination of the influence of the hydrogen subsystem on physicochemical properties and obtainment of materials for electrochemical devices. In contrast to other hydrogen-containing compounds, phase transitions in superprotonic crystals are accompanied by a radical change in properties, including the appearance of high proton conductivity at relatively low temperature (~400 K). Structural data on these crystals are indicative of the existence of different mechanisms of changes in physical properties [1]: the formation of a dynamically disordered system of hydrogen bonds as in M3H(XO4)2, crystallization water diffusion and formation of channels with partially occupied sites of atoms in (K,NH4)9H7(SO4)8·H2O [2], and the formation of a multiphase state. The transformation of bonds can stabilize the superprotonic phase and make it possible to supercool this phase practically to room temperature. Replacing ions with ammonium and the formation of additional hydrogen bonds can reduce conductivity in these crystals by four orders of magnitude or cause the occurrence of conduction already under ambient conditions. The kinetics of superprotonic phase transitions in Cs3(HSO4)2(H2PO4), Cs4(HSO4)3(H2PO4) and Cs6H(HSO4)3(H2PO4)4 crystals [3] depends on their structure and composition significantly. The kinetics of the phase transitions of Cs3(HSO4)2(H2PO4) and Cs4(HSO4)3(H2PO4) change considerably owing to the statistical replacement of PO4 tetrahedra by the SO4 groups and decreasing the number of hydrogen bonds. The Cs6H(HSO4)3(H2PO4)4 (Fig.) compound is chemically stable and exhibits reproducible properties. This study was supported by the DST-RFBR collaboration (No13-02-92693, INT/RFBR/P-140) and by the Scholarship of the President of the Russian Federation (no. SP-1445.2016.1).