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This review is devoted to a comprehensive analysis of DNA copy number variations (CNVs) identified in patients with neurodevelopmental disorders (NDDs) from the literature. The selection of publications was conducted using specifically developed criteria. CNVs were characterized based on their clinical significance, type of copy number alteration (microdeletion/microduplication), size, origin, and gene content. The study sample comprised 3375 patients with NDDs. Pathogenic and likely pathogenic CNVs, as well as variants of uncertain clinical significance, were identified in 395 individuals (12%). Chromosomal variations of each category were identified in 89 (3%), 56 (2%), and 241 (7%) patients, respectively. Nine individuals exhibited combinations of CNVs with different clinical significance. The number of duplications slightly exceeded the number of deletions (250 and 204, respectively). The size of most CNVs ranged from 193 bp to 400 kb and from 1 to 3 Mb (237 and 96, respectively). Seventy-two variants originated de novo, while 165 were inherited. Eighty-six CNVs were associated with 33 known microdeletion/microduplication syndromes. The most prevalent syndromes were 1q21.1 duplication (7/395, 1.8%) (OMIM: 612475), 2p16.3 deletion (9/395, 2.3%) (OMIM: 614332), 15q13.3 deletion (7/395, 1.8%) (OMIM: 612001), 16p11.2 deletion (9/395, 2.3%) (OMIM: 611913), and 22q11.2 duplication (7/395, 1.8%) (OMIM: 608363) syndromes. Enrichment analysis revealed that pathogenic CNVs, as well as variants of uncertain clinical significance, are enriched in genes associated with abnormal behavioral and neurological phenotypes. Likely pathogenic CNVs included genes associated with disorders of the nervous system and homeostasis/metabolism. [ABSTRACT FROM AUTHOR]

A brief history of the development of ideas about pleiotropy, its types, and the overall prevalence of pleiotropic loci in the human genome, as well as pleiotropic variants and genes within the same group of pathologies (disorders of psychomotor development) and between different diseases are discussed. Data on the association of the birth of a child with intellectual disability in a woman with a history of miscarriage are presented. The involvement of the same copy number variations (CNVs) in disorders of prenatal and postnatal development has been shown. The hypothesis is proposed that these CNVs are pleiotropic and manifested by one pathology or another, depending on additional modifying factors. [ABSTRACT FROM AUTHOR]

This review concerns the mechanisms of bacterial cell survival based on the induction of hibernation factors (HFs) that suppress protein synthesis via the inhibition of ribosomal functions. These factors include ribosome-binding proteins that inhibit 70S ribosomes (RaiA), form their inactive 100S dimers (RMF and HPF), or act at different stages of the translation cycle (RsfS, YqjD, SRA, and EttA). In some cells of the population, HFs cause the formation of a dormant state, which is characterized by a low rate of metabolic processes. This results in the tolerance of these cells and, as a consequence, the ability to persist in the presence of antibiotics and under stress conditions. The role of metabolic factors (polyamines and indoles) in the regulation of the expression levels of hibernation genes is discussed. [ABSTRACT FROM AUTHOR]

Human ring chromosomes are often unstable during mitosis, and daughter cells can be partially or completely aneuploid. We studied the mitotic stability of four ring chromosomes, 8, 13, 18, and 22, in long-term cultures of skin fibroblasts and induced pluripotent stem cells (iPSCs) by GTG karyotyping and aCGH. Ring chromosome loss and secondary aberrations were observed in all fibroblast cultures except for r(18). We found monosomy, fragmentation, and translocation of indexed chromosomes. In iPSCs, aCGH revealed striking differences in mitotic stability both between iPSC lines with different rings and, in some cases, between cell lines with the same ring chromosome. We registered the spontaneous rescue of karyotype 46,XY,r(8) to 46,XY in all six iPSC lines through ring chromosome loss and intact homologue duplication with isoUPD(8)pat occurrence, as proven by SNP genotype distribution analysis. In iPSCs with other ring chromosomes, karyotype correction was not observed. Our results suggest that spontaneous correction of the karyotype with ring chromosomes in iPSCs is not universal and that pluripotency is compatible with a wide range of derivative karyotypes. We conclude that marked variability in the frequency of secondary rearrangements exists in both fibroblast and iPSC cultures, expanding the clinical significance of the constitutional ring chromosome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The genomic architecture predisposed to the emergence of DNA copy number variation causing a new class of human chromosomal diseases-reciprocal microdeletion and microduplication syndromes- is reviewed in the paper. The molecular mechanisms of such chromosomal abnormalities are described. The problems of the interpretation of their clinical significance and genotype-phenotype correlations are discussed. The classification of phenotypes due to reciprocal chromosomal microdeletions and microduplications is shown. Published by 2015, reciprocal mutations associated with inherited and congenital human pathology and involving 58 chromosomal regions are summarized. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The methylation status of the cell cycle control gene RB1 has been studied in placental tissues of spontaneous abortions of the first trimester of pregnancy with mosaic variants of numerical chromosomal abnormalities verified by a molecular cytogenetic examination. Aberrant methylation of the gene promoter region has been revealed for the first time in 20% of embryos with chromosomal mosaicism that died in utero. A maximum frequency of epimutations was recorded in a group of embryos with a low level of abnormal cells for which mitotic errors are most likely to determine the formation of mosaic aneuploidy in primary euploid zygotes. It has been suggested that aberrant epigenetic genomic modifications at early stages of human embryonic development can be one of the mechanisms promoting genomic instability realized in the form of mosaic abnormalities of the karyotype that are incompatible with the normal course of embryogenesis. [ABSTRACT FROM AUTHOR]

Dimerization kinetics was studied for fullerene C[sub 60] 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 (C[sub 60])[sub 2] were obtained using its analytical IR band at 796cm[sup – 1]. Under the assumption that pressure-induced C[sub 60] 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) ×10[sup 14]s[sup –1], respectively. The specific features of the solid-phase C[sub 60] dimerization in simple cubic and face-centered cubic fullerite phases are discussed. © 2000 MAIK “Nauka / Interperiodica”. [ABSTRACT FROM AUTHOR]

The dimerization of C[sub 60] 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 (C[sub 60])[sub 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. © 1998 American Institute of Physics. [ABSTRACT FROM AUTHOR]

It is established by x-ray diffraction and Raman scattering that the polymerization of C[sub 60] 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 C[sub 60] polymers by the method of atom-atom potentials that the energetically favorable structure of the orthorhombic phase belongs to the space group Pnnm and not the previously proposed group Immm. 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. [ABSTRACT FROM AUTHOR]

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. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Differentiation of induced pluripotent stem cells (iPSCs) from patients and healthy donors allows in vitro study of genetic disorders. The authors have previously reported a clinical case of recurrent pregnancy loss in a patient with skewed X-chromosome inactivation in peripheral blood lymphocytes, endometrium, and buccal epithelium. A 239 kb microdeletion at Xq24 that affected eight genes, including UBE2A, has been found. In this work, an iPSC line iTAF15Xsk4 was produced from the patient's skin fibroblasts using nonintegrating episomal vectors. The iPSC line had a normal karyotype, expressed pluripotency markers, and expressed markers of all three germ layers upon differentiation in embryoid bodies. This cell line could be used for the UBE2A deficiency syndrome study. [ABSTRACT FROM AUTHOR]

Early stages of human embryonic development are characterized by the spatiotemporal 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, which affect the correct chromosome segregation during mitosis. In this study, a comparative analysis of the methylation index of LINE-1 retrotransposon, which largely reflects 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 studied groups. At the same time, the excessive hypomethylation of transposable genetic element was registered in spontaneous abortions with normal karyotype. We hypothesize that violations of parental genome demethylation during epigenetic reprogramming at preimplantation stages of development may be associated with an increased frequency of mitotic errors in chromosome segregation, which leads to the formation of a mosaic karyotype. [ABSTRACT FROM AUTHOR]

The presence of an extra chromosome in the embryo karyotype often dramatically affects the fate of pregnancy. Trisomy 16 is the most common aneuploidy in first-trimester miscarriages. The present study identified changes in DNA methylation in chorionic villi of miscarriages with trisomy 16. Ninety-seven differentially methylated sites in 91 genes were identified (false discovery rate (FDR) < 0.05 and Δβ > 0.15) using DNA methylation arrays. Most of the differentially methylated genes encoded secreted proteins, signaling peptides, and receptors with disulfide bonds. Subsequent analysis using targeted bisulfite massive parallel sequencing showed hypermethylation of the promoters of specific genes in miscarriages with trisomy 16 but not miscarriages with other aneuploidies. Some of the genes were responsible for the development of the placenta and embryo (GATA3-AS1, TRPV6, SCL13A4, and CALCB) and the formation of the mitotic spindle (ANKRD53). Hypermethylation of GATA3-AS1 was associated with reduced expression of GATA3 protein in chorionic villi of miscarriages with trisomy 16. Aberrant hypermethylation of genes may lead to a decrease in expression, impaired trophoblast differentiation and invasion, mitotic disorders, chromosomal mosaicism and karyotype self-correction via trisomy rescue mechanisms. [ABSTRACT FROM AUTHOR]

The article discusses a study regarding the reactions of benzaldehyde dimethylhydrazone with phosphorous acids. It says that the reactions of the obtained hydrazone, diethyl, and diphenyl phosphites were performed under different conditions, in which catalysts are used in the Pudovik reaction. It adds that the slow reaction of diphenyl phosphite with hydrazone I was accelerated by the introduction of trimethylchlorosilane.

Purpose: High frequency of aneuploidy in meiosis and cleavage stage coincides with waves of epigenetic genome reprogramming that may indicate a possible association between epigenetic mechanisms and aneuploidy occurrence. This study aimed to assess the methylation level of the long interspersed repeat element 1 (LINE-1) retrotransposon in chorionic villi of first trimester miscarriages with a normal karyotype and aneuploidy. Methods: The methylation level was assessed at 19 LINE-1 promoter CpG sites in chorionic villi of 141 miscarriages with trisomy of chromosomes 2, 6, 8–10, 13–15, 16, 18, 20–22, and monosomy X using massive parallel sequencing. Results: The LINE-1 methylation level was elevated statistically significant in chorionic villi of miscarriages with both trisomy (45.2 ± 4.3%) and monosomy X (46.9 ± 4.2%) compared with that in induced abortions (40.0 ± 2.4%) (p < 0.00001). The LINE-1 methylation levels were specific for miscarriages with different aneuploidies and significantly increased in miscarriages with trisomies 8, 14, and 18 and monosomy X (p < 0.05). The LINE-1 methylation level increased with gestational age both for group of miscarriages regardless of karyotype (R = 0.21, p = 0.012) and specifically for miscarriages with trisomy 16 (R = 0.48, p = 0.007). LINE-1 methylation decreased with maternal age in miscarriages with a normal karyotype (R = − 0.31, p = 0.029) and with trisomy 21 (R = − 0.64, p = 0.024) and increased with paternal age for miscarriages with trisomy 16 (R = 0.38, p = 0.048) and monosomy X (R = 0.73, p = 0.003). Conclusion: Our results indicate that the pathogenic effects of aneuploidy in human embryogenesis can be supplemented with significant epigenetic changes in the repetitive sequences. [ABSTRACT FROM AUTHOR]

Discusses the varied magnetic properties of the nanostructured forms of molecular carbon. Rise of superconducting and ferromagnetic properties in pure graphite; Features of typical ferromagnets; Indication of Curie temperature.

A letter to the editor is presented about high-temperature ferromagnetism in a polymeric phase of pure carbon that was free of ferromagnetic impurities.

Presents a correction to an article about magnetic carbon, previously published in the journal "Nature."