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Human induced pluripotent stem cells (iPSCs) are a promising source of cells for regenerative medicine, study of the pathogenesis of various diseases, screening of pharmacological drugs, and other clinical and basic research. However, the maintenance of the genetic stability of the cells during reprogramming, long-term culture, and directed differentiation is necessary for the use of iPSCs. Large chromosomal aberrations affect the quality of iPSCs most adversely, so the review focuses on the analysis of chromosomal abnormalities, including the recurrent aneuploidy; the sources of its origin, the effect of reprogramming, and long-term culture on the accumulation of chromosome aberrations are discussed. Cases of spontaneous correction of the iPSCs karyotype and the possibility of induced correction of the large chromosomal abnormalities by removing or silencing the extra homologue are considered.

Using chromosome microarray analysis, 52 samples of placental tissues from first trimester human spontaneous abortions were examined. One hundred twenty copy number variations (CNVs) were identified, affecting one or more genes (total of 427 genes). Using enrichment analysis with the mammalian phenotype ontology, all genes were divided into 183 categories (p ≤ 0.05). The embryogenesis category included 22 genes: AIP, BMP4, BMP5, CDKN1C, EXT1, GAB1, H19, HOXD13, IGF2, KIT, LDHA, NKX2-5, NRK, PEG3, PHLDA2, SMCHD1, SMN1, TBX3, TGIF1, TH, TLX2, and TRR. In this paper, the functions of each of the above genes and pathological phenotypes associated with mutations in them are discussed. A hypothesis of the pleiotropic effect of genes involved in CNVs in spontaneous abortions is proposed.

Analysis of the prevalence of copy number variations of the CNTN6 gene, recently selected as a new candidate gene for intellectual disorders, was performed. Real-time PCR did not detect any change in the number of CNTN6 gene copies in a group of 200 patients with impaired intellectual development. However, taking into account our data from the previous aCGH analysis and published data, the overall frequency of microdeletions and microduplications of CNTN6 was estimated as 1: 265 (0.4%). The common phenotypic features of 40 patients with microdeletions and microduplications of CNTN6 appeared to be the autism spectrum disorders, developmental delay, intellectual disability, seizures, cognitive impairment, cardiological defects, and behavioral problems.

Early stages of human embryonic development are characterized by spatio-temporal coincidence of events of total epigenetic genome reprogramming and elevated level of mosaic forms of numerical chromosome abnormalities. It is possible that the abnormal reprogramming of various regions of the genome can lead to violations of local epigenetic chromatin organization and gene expression, affecting the correct chromosome segregation during mitosis. In this study, a comparative analysis of the methylation index of LINE-1 retrotransposon, which is largely reflecting the methylation profile of the genome, is performed in placental tissues of spontaneous abortions with complete and mosaic forms of aneuploidy, and with a normal karyotype, as well as in the control group of induced abortions of the first trimester of pregnancy. It was shown that extraembryonic mesoderm and chorionic cytotrophoblast of spontaneous abortions with chromosomal mosaicism are characterized by the highest index of LINE-1 methylation among all groups studied. At the same time excessive hypomethylation of transposable genetic element recorded in spontaneous abortions with normal karyotype. It is suggested that violations of parental genomes demethylation during epigenetic reprogramming at preimplantation stages of development may be associated with an increased frequency of mitotic errors in chromosome segregation, leading to the formation of a mosaic karyotype.

The methylation profiles of the placental tissues of human embryos with normal karyotype and trisomy 16 were compared using an Infinium HumanMethylation27 BeadChip array (Illumina, United States). Numerous differences between the extraembryonic tissues with diploid and aneuploid karyotypes were observed. The extraembryonic mesoderm of embryos with trisomy 16 appeared to be less methylated than the diploid tissue, whereas the cytotrophoblast of aneuploid embryos was hypermethylated. The presence of the supernumerary chromosome was shown to influence the epigenetic profile of the genome by changing the level of methylation of CpG sites of all chromosomes. However, the largest number of differentially methylated loci was found on chromosome 16. Furthermore, more often, the epimutations were tissuespecific. In both tissues, the hypomethylated genes belong to the groups of genes responsible for different metabolic processes, whereas the hypermethylated genes control the processes of development, cell adhesion, immune response, and response to stimulus.

For the first time, DNA methylation patterns in the human cytotrophoblast and the extraembryonic mesoderm were determined using a genome-wide Infinium HumanMethylation27 BeadChip Array (Illumina, United States). These tissues are derivatives of the trophectoderm and the inner cell mass of the blastocyst and have substantial differences in the dynamics of epigenetic genome reprogramming during early stages of differentiation. It was shown that the genome of the extraembryonic mesoderm cells was more methylated than that of the cytotrophoblast, similarly to the findings in other mammalian species. There were differences in the methylation patterns of single CpG dinucleotides and dinucleotides located within promoter CpG islands: in both tissues most single CpG dinucleotides were methylated, promoters CpG island sites were not. A comparative analysis revealed 202 differentially methylated genes in the extraembryonic mesoderm and 40 such genes in the cytotrophoblast. These genes are responsible for a number of diverse biological processes. However, in the extraembryonic mesoderm, a majority of genes identified were responsible for DNA binding and transcriptional factor activity, whereas those identified in the cytotrophoblast were responsible for transport and protein and cytokine secretion.

Epigenetic mechanisms of cell cycle regulation providing for maintenance of genome stability and precise transmission of hereditary information to the daughter cells attract considerable interest. Up-to-date molecular technologies allow the genome-wide methylation pattern to be determined in a single experiment. In this work, we pioneered in determining the epigenetic status of the placental tissues of the human embryos with mosaic karyotype using a genome-wide Illumina Infinium HumanMethylation27 BeadChip array (Illumina, United States), comprising 27578 CpG dinucleotides contained in 14475 genes. The groups of genes associated with the cell cycle and its regulation that contain differentially methylated CpG sites in their promoter regions have been determined. It was demonstrated that the methylation level most frequently changed in oncogenes (ARHGEF1 and FGF5), tumor suppressors (APC2, BRACA2, DCC, GRLF1, RB1, TP73, TSPYL2, and VHL), and the genes involved in the regulation of chromosome segregation (CNTROB, GMNN, PROCR, and TACC1).

The sex ratio and X-chromosome inactivation were analyzed in placental tissues of human spontaneous abortuses with pure and mosaic forms of chromosome 16 trisomy. The sex ratio value was found to decrease with an increase in the share of cells with the trisomic karyotype, which suggests differential survival of embryos belonging to different sexes. The pattern of X-chromosome inactivation in cells of extraembryonic mesoderm in the control group of embryos and in spontaneous abortuses with the level of trisomy 16 below 80% corresponded to random X-inactivation, whereas in most embryos with a frequency of trisomy 16 exceeding 80% skewed inactivation was observed. Our results support the hypothesis about the existence of an autosomal transfactor influencing the initiation of X-chromosome inactivation and suggest its possible localization on chromosome 16.

The methylation status of the promoter region of the cell cycle gene P14ARF was studied in the extraembryonic mesoderm and in the cytotrophoblast of 46 human spontaneous abortions with chromosomal mosaicism. Aberrant methylation of alleles of this gene was revealed for the first time in placental tissues of 9% of embryos. The identified epimutations were found to be characteristic of embryos with aneuploid cell clones of postzygotic origin. It is suggested that epigenetic inactivation of loci responsible for the regulation of cell division and for segregation of chromosomes is associated with the origin of mosaic forms of the karyotype at early stages of human embryonic development.

Mass transfer to a horizontal electrode during electrolytic evolution of oxygen and hydrogen at current densities of 100 to 10 000 A/m2 is studied. The mass transfer intensity is evaluated from the diffusion layer thickness, which varies from 60 to 5 μm at such current densities. Calculations show that the decrease in the diffusion layer thickness is due to bubbles with a stationary interphase surface crossing the diffusion layer. During the hydrogen evolution, the diffusion layer thickness is nearly the same for vertical and horizontal electrodes. During the oxygen evolution, the diffusion layer is much thinner for a horizontal electrode. Additional decrease of the diffusion layer thickness during the evolution of oxygen is associated with the lesser solution density in the near-electrode layer and with its transport away by means of natural convection.

Trimethylchlorosilane is known to affect the reactions of phosphorous acids with olefins resulting in phosphonates. In particular, it reacts with diethyl phosphite to form trimethylsilyldiethyl phosphite and hydrogen chloride, changing pH of the medium. It is known that the presence of acidic impurities in phosphoric acids promoted the phosphonates formation [4]. Basing on that knowledge, we introduced the catalytic amount of trimethylchlorosilane to the reaction of benzaldehyde dimethylhydrazone I with diethyl phosphite. As a result, diethyl(1-phenyl-1-dimethylhydrazino)phosphonate II was isolated in the form of white crystalline substance. Its structure was confirmed by elemental analysis, IR, and P NMR spectroscopy data. I C O

Dimerization kinetics was studied for fullerene C60 by IR spectroscopy at a pressure of 1.5 GPa in the temperature range 373–473 K. The kinetic curves for the formation of a dimer (C60)2 were obtained using its analytical IR band at 796 cm−1. Under the assumption that pressure-induced C60 dimerization is a second-order irreversible reaction, the reaction rate constants were determined at different temperatures. The corresponding activation energy and preexponential factor were found to be 134±6 kJ/mol and (1.74± 0.24)×1014 s−1, respectively. The specific features of the solid-phase C60 dimerization in simple cubic and face-centered cubic fullerite phases are discussed.

The dimerization of C60 fullerene under conditions of quasi-hydrostatic compression at temperatures above 293 K is investigated by IR spectroscopy, Raman scattering (RS) spectroscopy, and x-ray diffraction. The measured dimer (C60)2 content in the products of the polymerization of fullerite as a function of the pressure, temperature, and treatment time shows that dimerization occurs even at room temperature in the entire pressure range above ∼1.0 GPa. However, at least at temperatures above 400 K dimerization does not result in the formation of a dimer phase as a stable modification of the system, since the dimer is an intermediate product of the transformation. It is shown that increasing the holding time at 423 K decreases the content of the dimer fraction in the samples and results in the formation of linear (at 1.5 GPa) and two-dimensional (at 6.0 GPa) polymers, which are structure-forming elements of the orthorhombic and rhombohedral polymerized phases.

It is established by x-ray diffraction and Raman scattering that the polymerization of C60 fullerene at 1.5 GPa and 723 K leads to the formation of an orthorhombic phase that is different from the previously identified high-pressure orthorhombic phase. It is determined by a calculation of the optimal packing of linear C60 polymers by the method of atom-atom potentials that the energetically favorable structure of the orthorhombic phase belongs to the space group P n n m and not the previously proposed group I m m m. The computed value of the rotation angle of the polymer chains that corresponds to the minimum packing energy was equal to 61°. The mechanisms leading to the formation of the polymerized phases are discussed on the basis of the results obtained.

Modifications of carbon which are formed from C60 fullerite at pressures up to 10.0 GPa and temperatures up to 1900 K are studied by x-ray diffraction, Raman spectroscopy, and atomic force microscopy methods. The pressures p and temperatures T at which atomic, molecular, and polymolecular structures form under conditions of quasihydrostatic compression are determined. It is shown that, together with polymerization, another type of chemical interaction of the molecules, called polycondensation, which leads to the formation of polymolecular structures with a shortest intermolecular distance of 0.65 nm, is possible in the system. Three-dimensional polycondensation of C60 fullerene is explained by the special properties of the new carbon states.

The kinetics of fullerene solid-phase dimerization proceeding through the 2+2 cycloaddition of C60 at a pressure of 1.5 GPa is investigated by vibrational spectroscopy in the temperature range 373–473 K. Kinetic curves for the formation of (C60)2 dimers are obtained using the analytical band at 796 cm−1 in the IR spectra of the (C60)2 dimer molecule. Under the assumption that the pressure-induced dimerization of C60 is an irreversible second-order reaction, the reaction rate constants are determined at different temperatures. The activation energy and the preexponential factor are found to be equal to 134±6 kJ/mol and (1.74±0.24)×1014 s−1, respectively.