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The features of the coupled aldol condensation—hydrogenation processing of ethyl methyl ketone on a Pd/activated carbon catalyst were studied. The phase and chemical composition of activated carbon, as well as the carbon based catalyst, were studied using powder X-ray diffraction and electron microscopy. We established the influence of the reaction temperature, palladium mass content, contact time, and H2/EtC(O)Me molar ratio on the main parameters of the process, namely, on the conversion of the starting EtC(O)Me and the selectivity of the formation of 5-methylheptan-3-one and 3-methylheptane. The optimal process conditions were selected (0.3 wt.% of palladium, 300 °C, contact time 17 s, a 1.25 H2/EtC(O)Me molar ratio), allowing to achieve a 96% total selectivity for the target products. [ABSTRACT FROM AUTHOR]

Leptin, secreted by adipose tissue, indirectly stimulates the activity of GnRH-producing neurons in the hypothalamus and thus regulates the functional activity of the hypothalamic–pituitary–testicular (HPT) axis. Obesity is known to be accompanied by a systemic hyperleptinemia and impaired leptin transport in the central nervous system, which limits the use of full-length leptin as a drug. It was previously shown that the intranasally administered (i.n.) leptin fragment MA-[D-Leu4]-OB3 (LF) enhances the steroidogenic effect of human chorionic gonadotropin (hCG) in rats fed a standard diet. An even more urgent task is to assess its effect on testicular steroidogenesis in obesity that reduces reproductive functions in men. This work was aimed to study the ability of LF (200 µg/kg, i.n., for 3 days) to modulate the effect of hCG (10 IU/rat, s.c., once) on testicular steroidogenesis in male Wistar rats with obesity induced by a 20-week high-fat/high-carb diet (HFHCD), as well as to evaluate the impact of the GnRH receptor antagonist Cetrorelix (ANT, 75 µg/kg, s.c., for 3 days) on the effects of LF in these animals. Obese rats demonstrated reduced testicular levels of the luteinizing hormone receptor (LHR) and a compensatorily upregulated expression of the Cyp11a1 gene encoding the steroidogenic enzyme cytochrome P450scc. LF administration enhanced hCG effects on blood testosterone levels and testicular expression of the Star gene encoding the cholesterol transporter protein StAR, which suggests the ability of LF to positively modulate HPT axis activity under obesity. ANT and LF co-administration, by contrast, reduced the stimulatory effect of hCG on blood testosterone levels and testicular Star gene expression, which may be due to the testicular effects of LF. Our data indicate the ability of LF to influence different components of the male gonadal axis under conditions of diet-induced obesity. [ABSTRACT FROM AUTHOR]

The Cretaceous Normal Superchron (CNS, 84–121 Ma) is a singular period of the geodynamo's history, identified by a prolonged absence of polarity reversals. To better characterize the paleosecular variation (PSV) of the geomagnetic field at the end of this interval, we sampled seven continuous sequences of lava flows from the Okhotsk‐Chukotka Volcanic Belt, emplaced 84–89 Ma in the vicinity of the Kupol ore deposit (NE Russia). From a collection of 1,024 paleomagnetic cores out of 82 investigated lava flows, we successfully determined the paleodirections of 78 lava flows, which led to 57 directional groups after removing the serial correlations. The resulting paleomagnetic pole is located at 170.0°E, 76.8°N (A95 = 5.2°, N = 57), in good agreement with previous estimates for north‐eastern Eurasia. Aiming at quantifying PSV at a reconstructed paleolatitude (λ) of ∼80°N, we obtained a virtual geomagnetic pole (VGP) scatter Sb=21.5°|19.3°24.0°(N=57) ${{S}_{\mathrm{b}}=21.5{}^{\circ}\vert }_{19.3{}^{\circ}}^{24.0{}^{\circ}}\,(N=57)$, the value of which was corrected for within‐site dispersion and is little dependent on the choice of the selection criteria. Compared to previous paleodirectional data sets characterizing PSV at various paleolatitudes during the CNS, our Sb estimate confirms a relative latitudinal increase Sb(λ = 90°)/Sb(λ = 0°) on the order of 2–2.5. Focusing on PSV at high paleolatitude within the 70°–90° range, we show that Sb was ∼15% lower at the end of the CNS than during the past 10 Myr, confirming that the singular polarity regime of the geodynamo observed during the CNS is likely accompanied with reduced PSV. Plain Language Summary: Compared to the last 10 million years during which Earth's magnetic field stochastically reversed its polarity ∼4 times per million year, the Cretaceous Normal Superchron (CNS, 84–121 Ma) represents an anomalously long period of stable polarity, the understanding of which is crucial to constrain the working of the geodynamo. In this effort to better characterize the paleosecular variation (PSV) of the geodynamo, we investigated the paleomagnetic record of lava flow sequences from the Okhotsk‐Chukotka Volcanic Belt (NE Russia) emplaced 84–89 Ma at high paleolatitude. First, we obtained that the dispersion of virtual paleomagnetic poles (VGP), used as a proxy for PSV, is 2–2.5 times as high at the paleopole as at the paleoequator. Second, we showed that VGP scatter at high paleolatitude was ∼15% lower at the end of the CNS than during the last 10 million years, confirming a potential link between polarity regime and PSV. Key Points: We investigate geomagnetic field behavior at high paleolatitude (∼80°N) at the end of the Cretaceous Normal Superchron (CNS)We present a paleodirectional data set from 78 lava flows (resp. 57 directional groups), emplaced 84–89 Ma in north‐eastern EurasiaWe show that the dispersion of virtual geomagnetic poles at high latitude is ∼15% lower during the CNS than for the past 10 Myr [ABSTRACT FROM AUTHOR]

In this paper, a cellular automation model developed on the basis of Bezier curves with the use of a cellular automation approach for the creation of digital twins for porous nanostructures of different nature is proposed. Some numerical experiments on the creation of digital twins for the synthesized experimental samples of chitosan-based aerogels are carried out. The structural characteristics of the digital copies and experimental samples are compared, allowing us to conclude that the model is correct. The resulting digital twins can be used for predicting the properties of porous fiber materials, in particular, chitosan-based aerogels, to provide the partial replacement of real experiments by computational ones and, consequently, to decrease the expenditures on the development of new materials with specified properties. [ABSTRACT FROM AUTHOR]

The adipokine leptin plays an important role in the regulation of the reproductive system. It stimulates the activity of the hypothalamic–pituitary–gonadal axis by indirectly affecting gonadoliberin (GnRH)-secreting neurons and modulates testicular steroidogenesis via binding to leptin receptors in Leydig cells. The leptin fragment (LF) 116–122, which includes the main receptor-binding determinants of this adipokine, normalizes metabolic parameters in animals with a diet-induced obesity. However, its ability to influence the testicular steroidogenic function, including through interaction with hypothalamic GnRH neurons, has not been studied. The aim of this work was to study the effects of a single and 3-day intranasal LF administration (200 µg/rat) on blood testosterone levels and expression of steroidogenic genes in the testes of mature male Wistar rats, as well as to evaluate the steroidogenic activity of LF upon testosterone synthesis stimulation by human chorionic gonadotropin (hCG, 15 IU/rat, s.c.) and inhibition by the GnRH receptor antagonist Cetrorelix (75 µg/kg, s.c.). It was shown that a single LF administration increases blood testosterone levels, while a 3-day administration enhances the steroidogenic effect of hCG. LF and hCG increased the expression of the Star gene that encodes the key regulatory protein of steroidogenesis StAR. Cetrorelix administration reduced blood testosterone levels and Star expression, while compensatory increasing gene expression of the luteinizing hormone receptor. The potentiating effect of LF on hCG-induced stimulation of testosterone synthesis and Star expression was not detected after Cetrorelix treatment. Thus, LF is able to stimulate testicular steroidogenesis in rats by itself and potentiate the steroidogenic effects of hCG. Since its effects are suppressed in the presence of a GnRH antagonist, there are grounds to assume that they are implemented via stimulation of hypothalamic GnRH neurons. [ABSTRACT FROM AUTHOR]

Most copy number variations (CNV) of pathogenetic significance are associated with neurodevelopmental phenotypes and characterized by incomplete penetrance and variable expressivity. However, the nature of these phenomena has not yet been disclosed. As a result, this leads to the uncertainty of prognosis in families with affected children having a genetic variant associated with the disease that was, however, inherited from apparently healthy parents, which is a problem for genetic counseling in medicine. This review discusses the evidence for the contribution of interloci interaction between different CNVs to variability of clinical manifestations of neuropsychiatric and intellectual disorders. [ABSTRACT FROM AUTHOR]

Abstract—A paleomagnetic study of the Okhotsk–Chukotka belt volcanics exposed in the region of the Kupol field (~66.9° N, 170.1° E) has been carried out. The studied rocks were formed between 85 and 95 Ma during the Cretaceous Normal Superchron (CNS). In most of the studied samples, the characteristic magnetization component is isolated. Its primary origin is supported by the positive fold test, magnetic mineralogy data, and similarity of the calculated paleomagnetic pole with that of coeval rocks from the same region. It is shown that the studied rocks were formed in high polar latitudes close to 80° N. The amplitude of paleosecular variation (PSV) of the geomagnetic field during CNS has been estimated. Depending on the calculation method, the estimates (and their confidence intervals) for ~81° N are Sb = 22.1° (19.5°; 24.7°) in case of using a fixed cut-off angle of 45° and Sb = 23.1° (20.3°; 25.7°) in case of the cut-off angle calculated by the Vandamme method. The obtained estimates generally support the existing models of PSV latitudinal dependence for CNS. At the same time, the estimates are less consistent with the model (McFadden et al., 1991) where PSV values are low at the equator and sharply increase with latitude than with the model (Biggin et al., 2008) predicting higher PSV values at the equator and their more gentle increase towards polar latitudes. Irrespective of the calculation method, the obtained estimates almost perfectly fit the PSV latitudinal dependences for the last 5 Ma. This means that the amplitude of secular geomagnetic variation during CNS, at least at high latitudes, was the same as it was during the last 5 Ma. The obtained result does not support the hypothesis that geodynamo regimes change at the transition from the periods of frequent geomagnetic reversals to superchrons (e.g., (Gallet and Pavlov, 2016)), which suggests, in particular, that the modern numerical models are not fully adequate to the real processes of generation of the geomagnetic field. [ABSTRACT FROM AUTHOR]

U–Pb and 40Ar/39Ar age data obtained for volcanic rocks of the Okhotsk–Chukotka Belt in the headwaters of the Malyi Anyui River (the vicinity of Kupol deposit) indicate at least two main pulses of volcanic activity, 98–93 Ma and 90–84 Ma. The conventional stratigraphic models are not consistent with the new data on the age and composition of volcanic units. The spatial relations between volcanic complexes of different ages imply that volcanic units accumulated under conditions of dissected topography. In the absence of obvious petrographic distinctions between the volcanic sequences of different ages, the composition of detailed geological and paleovolcanological maps requires representative precise isotopic age data. [ABSTRACT FROM AUTHOR]

New U–Pb and 40Ar/39Ar isotopic dates on volcanic rocks of the East Chukotka segment of the Okhotsk–Chukotka Belt correspond to 76–71 Ma span, which is partially beyond the conventional lifetime of this volcanic province. This could result from the migration of magmatic loci along the strike of the volcanic belt, and/or from the overprint by a younger magmatic event. [ABSTRACT FROM AUTHOR]

Processes of trans–cis isomerization of azobenzene (AZB), 4,4′-azopyridine (AZP), and azoxybenzene (AZOB) are studied using quantum chemical calculations at the DFT/B3LYP/cc-pvTZ level of theory. The chosen objects can serve as reference points when studying intramolecular rearrangements of numerous compounds containing an azo group and an azoxy bridging group. Geometric and electronic characteristics of trans and cis isomers AZB and AZP and four AZOB isomers, as well as transition states (TSs) between them, are determined. It is established that two AZOB isomers containing a semi-polar bond N→O have a significantly lower energy than two isomers with a cyclic NON bridging group. The transition between the low-energy trans–cis isomers proceeds via a TS while preserving the N→O bond so that the oxygen atom does not migrate between the nitrogen atoms. The NBO analysis of the electronic structure is performed, the factors stabilizing the obtained geometric configurations of all isomers and transition states are determined. [ABSTRACT FROM AUTHOR]

The identification of the cybersecurity (CS) state of Internet of things (IoT) devices determines the necessity to search for and improve approaches to detecting various threat types. The unification used in the mass development of IoT devices facilitates software and hardware modification to block certain built-in protective functions from the side of a potential intruder. A need arises to develop universal methods for identifying the cybersecurity state of devices using comprehensive approaches to analyzing data from internal and external information channels. The article presents an approach to identifying the cybersecurity of IoT devices based on processing time series recorded from sensors during various processes, and internal and external (thirdparty) sources. The approach is based on classification methods. The presented solution uses template sequences containing synchronized time series showing numerical values obtained from various probes and sensors during process execution. The proposed approach makes it possible to identify IoT device cybersecurity states without increasing the volume of information stored and processed in internal resources. [ABSTRACT FROM AUTHOR]

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]

Abstract—Paleomagnetic studies of several Late Cretaceous volcanic sections of the Okhotsk–Chukotka volcanic belt have been carried out in the Bilibino region of the Chukotka Autonomous Okrug and along the Pevek–Egvekenot road. Extensive collections have been acquired and analyzed. The laboratory experiments isolated the ancient characteristic magnetization component reflecting the direction of the geomagnetic field at the time of formation of the studied rocks (~85 Ma ago). The primary character of the revealed characteristic magnetization component is supported by the positive regional fold test and by the coincidence of the paleomagnetic pole calculated from this component with that previously obtained for Chukotka from the rocks of similar age (Stone et al., 2009). The paleomagnetic pole calculated from the combination of the previous and our newly obtained data (Plat = 69.3°, Plong = 180.7°, N = 99, A95 = 5.1°) indicates that the sampled rocks were formed in the immediate vicinity of the geographic pole. The reliability of the existing Late Cretaceous paleomagnetic poles for Eurasia and North America is analyzed, and the refined poles are calculated for these plates for the time of ~85 Ma. The reconstruction of the Chukotka–Kolyma–Omolon block's position relative to Eurasia and North America allowing for the paleomagnetic poles calculated for that time is proposed. The reconstruction implies that from the formation time of the studied rocks up to the present, the Chukotka–Kolyma–Omolon block has undergone relatively small (tens to first hundreds of km) southward movements relative to the North American plate and has been noticeably shifted (by a few hundred km) relative to the Eurasian plate. Our reconstruction is close to that proposed in (Otofuji et al., 2015) but, in contrast to the latter, it does not require a collision between the Chukotka–Kolyma–Omolon block and Eurasia after 80 Ma ago. [ABSTRACT FROM AUTHOR]

Genomic imprinting is an epigenetic phenomenon that differentiates maternal and paternal copies of genes in the genome and causes monoallelic expression depending on parental origin. Imprinting is an evolutionary puzzle, as it bears the costs of diploidization without its advantages, namely, protection from recessive mutations. The aim of this review is to answer the question of why genomic imprinting arose and became fixed in the evolution of angiosperms, insects, marsupials, and placental mammals. [ABSTRACT FROM AUTHOR]

The aspects of transcriptional profiles of cells with chromosomal imbalance are discussed. There are certain difficulties in the assessment of phenotypic manifestations of chromosomal and genomic mutations. The data on the use of whole transcriptome analysis as an important new tool for investigation of the pathogenesis of chromosomal diseases related to aneuploidies, as well as microdeletion and microduplication syndromes, are described. The general patterns of gene expression changes in cells with chromosomal imbalance are highlighted: global dysregulation of gene expression; the similarity of transcriptional changes in cells with different aneuploidies or reciprocal copy number variations; common biological pathways and processes affected by mutations; the accumulation of transcriptional changes during ontogenesis. [ABSTRACT FROM AUTHOR]

Differential gene expression during development is maintained by complex regulatory epigenetic mechanisms that provide the formation of different specialized cell types. Subsequently, a multicellular organism is a mosaic of cells with differing epigenetic characteristics. It seems likely that exceeding the limits of normal epigenetic variability may cause the occurrence of pathological mosaic states in which one part of the cell population has a normal epigenotype, while the other part carries modified epigenetic information. In this review, using the genomic imprinting as a classical epigenetic phenomenon, for the first time, the prevalence of epigenetic mosaicism and the mechanisms of its origin, as well as its role in the etiology of hereditary disorders, determined by the dysfunction of imprinted genomic loci are summarized. [ABSTRACT FROM AUTHOR]

A procedure was suggested for preparing brominated polyols of reduced viscosity for the synthesis of foamed polyurethanes of reduced flammability. The flame-retarding action of the synthesized polyol tetrabromophthalate in polyurethane was studied in comparison with that of other widely used flame retardants. Evaluation of the effect exerted on the flammability of the polurethane compound by the polyol tetrabromophthalate synthesized, melamine, and aluminum hydroxide shows that all the samples containing flame retardants are self-extinguishing. The shortest combustion time was observed for the sample containing 6% polyol tetrabromophthalate synthesized. The sample containing as a flame retardant additive solely the synthesized polyole tetrabromophthalate also exhibits the highest performance as a heat-insulating material from the viewpoint of thermal conductivity. [ABSTRACT FROM AUTHOR]

Aim: The aim of study was to investigate the opportunities of local phlebectomy in the elimination of isolated pelvic-perineal reflux (PPR), as well as to determine the feasibility of endovascular embolization of the tributaries of internal iliac veins in PPR. Clinical trial no. NCT01598051.Materials and methods: The work is based on the results of examination and treatment of 43 female patients with varicose veins of the pelvis, perineum, and lower extremities. Patients had no signs of pelvic congestion syndrome (PCS). All patients underwent duplex ultrasound scanning (DUS) and ovariography with pelvic phlebography (OPP). For the elimination of PPR, local phlebectomy was performed in the major labia and perineal area, with maximal possible mobilization of the vessel within the operative wound (33 patients). In 10 patients with isolated varicose transformation of the superficial veins on the posterior thigh, mini-phlebectomy was performed using the Varady phlebectomy extractors.Results and discussion: The varicose syndrome of the external genitalia, perineum, and posterior thigh was successfully treated in 100% of patients. Findings suggest that thorough mobilization and excision of the veins of the pudendal labia, perineum, and subcutaneous veins of the thigh is a reliable method for eliminating the pathological reflux from the intrapelvic veins to the superficial veins of the perineum and lower extremities. No recurrences of vulvar, perineal varices or dilation of the veins of the lower extremities were observed in 100% of patients over the 3-year follow-up period.Conclusion: Local phlebectomy is an effective technique for eliminating the isolated PPR in patients with varicose transformation of intrapelvic, vulvar, or perineal veins. Endovascular embolization of the tributaries of the internal iliac veins is not an essential component in the treatment of PPR. The present study has a limitation due to the absence of patients with PCS. The effectiveness of phlebectomy in the treatment of isolated PPR was studied. [ABSTRACT FROM AUTHOR]

Men with obesity demonstrate not only various metabolic disorders and insulin resistance, but also reduced testosterone levels and reproductive system dysfunctions. Although one of the ways for pharmacological correction of these abnormalities may be the use of luteinizing hormone receptor (LHR) agonists and antidiabetic drugs (specifically, metformin, MF), the mechanisms of their effects on the hypothalamic–pituitary–gonadal axis have not been sufficiently investigated. The aim of this work was to study the effects of long-term MF therapy (5 weeks, 120 mg/kg) and five-day treatment with LHR agonists, such as human chorionic gonadotropin (hCG, 20 IU/rat/day, s.c.) and allosteric agonist TP03 (15 mg/kg/day, i.p.), on blood testosterone levels and the expression of testicular and pituitary genes in male Wistar rats with long-term diet-induced obesity (DIO). TP03 moderately stimulated testosterone production in male rats with DIO without having an inhibitory effect on testicular LHR expression and only insignificantly reducing the pituitary expression of the LH β-subunit gene. After a single TP03 administration to DIO rats, its steroidogenic effect was comparable to that in the control group, but after a five-day administration, it was significantly inferior to it. In DIO rats, the steroidogenic effect of hCG after a single administration was lower than that in the control but comparable to that after a five-day administration, significantly exceeding the corresponding effects of TP03. Unlike TP03, hCG significantly reduced testicular LHR expression and more pronouncedly inhibited pituitary LH expression. MF treatment restored the androgenic status without significantly affecting the testicular expression of steroidogenic genes. In MF-treated groups, there was no increase in the steroidogenic effects of both LHR agonists. The results suggest the prospects for the use of TP03 and hCG to stimulate testicular steroidogenesis and increase the effectiveness of MF therapy in order to normalize testosterone production in DIO, which can be used to correct reproductive disorders in obesity. At the same time, a co-administration of MF and LHR agonists in DIO appears to be inappropriate. [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]

The discovery of cell-free DNA in the blastocoele fluid is promising for the development of new noninvasive methods for the preimplantation genetic diagnosis of chromosomal diseases. However, there are no data confirming the concordance between the molecular karyotype of cell-free DNA from blastocoele fluid and the blastocyst cells per se. This paper reports on such concordance according to the results of molecular cytogenetic analysis by comparative genomic hybridization. [ABSTRACT FROM AUTHOR]

The biased expression of parental alleles plays a fundamental role in the formation of the placenta as a multifunctional organ necessary for the development and survival of the fetus. First of all, this is expressed in the phenomenon of imprinting, where only a maternal or paternal allele is expressed in placental cells. The placenta uses an extended range of imprinting mechanisms compared to the embryo: histone modifications that suppress or, conversely, activate the expression of nearby genes, regulatory sequences and genes derived from retroviruses or retrotransposons, which are microRNAs that function as antisense RNAs and participate in transcriptional and post-transcriptional regulation of gene expression. In addition, incomplete suppression of the activity of one of the parental alleles is detected in the placenta, leading to a biased imprinted expression of some genes. This review shows the role of biased expression of parental alleles in the development of placental structures of an embryo, discusses the mechanisms of epigenetic control of parental alleles, mainly expressed in the placenta. [ABSTRACT FROM AUTHOR]

The contribution of chromosomal abnormalities to recurrent pregnancy loss (RLP) is reviewed in the paper. Data from conventional cytogenetic analysis of the karyotype of parents and spontaneous abortions, as well as the results of molecular cytogenetic investigations and preimplantation genetic diagnostics, are discussed. Information about the significance of epigenetic impairments (abnormalities of imprinting and X-chromosome inactivation) for recurrent pregnancy loss is also considered. Cytogenetic analysis of products of conception enables ascertainment of the causes of embryonic death in a large proportion of families, more accurate estimation of the therapeutic efficiency of treatment and drugs (when women with abnormal embryos were excluded), and a statistically valid prognosis about the next pregnancy outcome. [ABSTRACT FROM AUTHOR]

This article examines the warming of steel in a tundish during the continuous casting of grades of steel that are used in critical applications. The authors examine how the introduction of an organic addition to the powdered slag-forming mixture affects its thermal conductivity. Quantitative relations are obtained to describe the dependence of the thermal conductivity and bulk density of the mixture on its content of rice husks. A comparative analysis of the warming properties of heat-insulating mixtures used at the leading Russian combines and powdered assimilating mixtures containing rice husks shows that the latter can be used without additional insulation. [ABSTRACT FROM AUTHOR]

The question is considered of assimilating non-metallic inclusions from metal by slag in a tundish during steel casting intended for cold rolling. The authors study changes in slag composition in a tundish and develop new assimilating mix compositions. Proceeding from results of laboratory study of physiochemical properties of the mixes developed, the authors recommend an assimilating mix for industrial tests. It is established that the rate of non-metallic AlO inclusion absorption by in the given mix is several times higher than for the standard mix used. [ABSTRACT FROM AUTHOR]

The involvement of the caudal hippocampus in spatial learning is presently uncertain, compared to the well established role of the dorsal region. Therefore voles ( Clethrionomys glareolus) with large (about 1/3 of the whole hippocampus) caudal cytotoxic lesions were tested in the Morris water maze. A version of the test intended to measure long term spatial memory was used. The lesion inhibited the learning process, as well as reducing the accuracy of platform location memory at early stages of training. The data obtained indicate the involvement of this area in control of spatial learning in rodents. [ABSTRACT FROM AUTHOR]

Chromosomal mosaicism is the presence of 2 or more cell lines with different karyotypes in the same individual. Mosaic karyotypes are a remarkable feature of early stages of human embryo development. They result from mitotic errors in chromosome segregation and demonstrate the clearest example of somatic mutagenesis in human beings. This review is devoted to the classification of chromosomal mosaicism and the analysis of its underlying mechanisms, incidence and phenotypic effects during embryo development. A model for tissue-specific aneuploid cell line compartmentalization in spontaneous abortions is introduced. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Disturbance of the epigenetic status of the H19 and KCNQ1OT1 imprinting centers of chromosome 11 and the CDKN1C imprinted gene in early human embryolethality have been studied. This is the first study to detect hypomethylation of KCNQ1OT1 in the maternal homolog in placental tissues from some (9.5%) spontaneous abortions with impaired cell proliferation during the first trimester of pregnancy. Tissue specificity of the aberrant methylation status of the imprinting center has been found. A hypothesis on the postimplantation origin of epimutations in somatic cells of the developing embryo is put forward. The selective role of epimutations of imprinted genes in early human ontogeny as compared to uniparental disomy is considered; estimation of the epigenetic risk entailed in using assisted reproductive technologies is discussed. [ABSTRACT FROM AUTHOR]

Genomic imprinting is an epigenetic phenomenon characterized by monoallelic expression of the genes depending on their parental origin. The molecular basis of this expression is covalent modifications of DNA and histones that are formed during maturation of germline cells. Abnormalities of the establishment of genomic imprinting during gametogenesis or its maintenance at various stages of development, caused by aberrant epigenetic modifications of the chromatin, predominantly disturbance of DNA methylation state, are a form of mutational variability of imprinted genomic loci. In this review, we consider the spectrum of epimutations of imprinted genes, present their classification, and discuss possible causes of their appearance and their role in etiology of hereditary human diseases. [ABSTRACT FROM AUTHOR]

To date, a wide range of assisted reproductive technologies is available for patients with impaired fertility. In general, the current methods of reproductive medicine are considered safe and do not significantly increase the frequency of birth of children with diseases or congenital malformations. However, the evidence has been accumulating in literature on higher risk of genomic imprinting diseases (Beckwith-Wiedemann and Angelman syndromes) as a result of using assisted reproductive technologies. In most cases examined, the appearance of these syndromes was explained by defective methylation status of imprinted genes. It has been suggested that manipulations with gametes and embryos during the period of total epigenetic modification of their genomes may act as potential risk factors of assisted reproductive technologies. Moreover, overcoming many natural reproductive barriers may contribute to the development of some pathological phenotypes. The review summarizes current views on epigenetic risk factors associated with assisted reproductive technologies. [ABSTRACT FROM AUTHOR]

We have previously reported a high rate of tetranucleotide DNA repeat mutations, including mutations of both germline and somatic origin, in spontaneous human abortions. To analyze in more detail mutational microsatellite (MS) variability in meiosis and its possible association with disturbed embryonic development, we have conducted a comparative study of mutation rates of a panel of 15 autosomal tetranucleotide MSs in 55 families with healthy children and in 103 families that have had spontaneous abortions with normal karyotypes. In the families with miscarriage, the gametic MS mutation rate was higher than in the families with normal reproductive function (4.36 × 10−3 versus 2.32 × 10−3 per locus per gamete per generation), but this difference was statistically nonsignificant ( P = 0.25). No association of MS mutations with familiar miscarriage was found. Mutations at the MS loci studied were recorded almost 3 times as often in spermatogenesis as in oogenesis, which is likely to result from a greater number of DNA replication cycles in male germline cell precursors than in female ones. Mutations increasing and reducing the MS sequence length appeared at virtually the same rate. Changes in MS DNA sequence length per one repeated element, i.e., single-step mutations (93% of cases) exceeded all other events of allele length change. The highest number of mutations (81.2%) was found in longer alleles. This distribution of mutations by size, direction, and parental origin corresponds to the multistep mutation model of their emergence via mechanism of DNA strand slippage during replication. [ABSTRACT FROM AUTHOR]

Analyzes all types of low-frequency spectra in radio-electronic devices in terms of classical single-mode electric circuits with lumped parameters. Study of a linear electric two-terminal network; Use of a harmonic probing signal generated in the continuous mode by an independent generator.

The results of standard cytogenetic analysis of the long-term cultures of embryonic fibroblasts of 478 first-trimester spontaneous abortions were retrospectively reviewed. In 16% of embryos with cytogenetically confirmed karyotype 46,XX, the Y chromosome was found by molecular genetic methods. Prior to obtaining the chromosome preparations, the cell cultures of Y chromosome-carrying embryos were maintained for a longer period than the cultures of embryos without the Y chromosome. Thus, a late entry of a culture into the log-growth phase serves as marker of maternal cell contamination. We developed a mathematical model for assessment of karyotype incidence and the “sex ratio” of spontaneous abortions, taking into account risk of maternal cell contamination in extraembryonic tissue cultures. Thus estimated, the incidence of chromosomal abnormalities in the studied sample increased from 54.6 to 60.3% and the expected sex ratio increased from 0.66 to 1.02 in abortions with normal karyotype. Using molecular analysis of inheritance of polymorphic DNA markers of six autosomes (2, 11, 16, 19, 20, and 21), the proposed model was tested on 60 embryos with karyotype 46,XX and their parents. Numerical chromosome abnormalities were revealed in uncultured tissues of seven abortions (11.7%), including four without the Y chromosome, which is in a good agreement with the expected incidence of karyotype abnormalities (8.3%) predicted by our model. In view of this, estimating risk of maternal cell contamination in embryonic cell cultures seems necessary for correctly assessing the effect of natural selection in humans, for understanding the mechanisms that determine the sex ratio, and for evaluating the accuracy of prenatal cytogenetic diagnosis of chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

Autosomal monosomies represent a severe form of genomic disbalance which determines elimination of human embryos already at the preimplantation stages. As a rule, they occur very rarely in the materials of spontaneously aborted embryos and fetuses. Molecular-cytogenetic studies were carried out on the karyotype of cells of 60 spontaneous abortuses of I trimester of pregnancy with cell degeneration or absence of cell proliferation in the cultures, as a result of which the cells could not be studied using the standard metaphase analysis. The embryos were characterized by an unexpectedly high frequency of mosaic variants of monosomies for chromosomes 7, 15, 21, and 22, which amounted to 19% of all chromosome aberrations. Lethal forms of monosomies for human chromosomes 7 and 15 were described for the first time, since they are not found in spontaneous abortuses by standard cytogenetic methods. A hypothesis was proposed which accounts for the possibility of early postimplantation lethality of the embryos with mosaic forms of autosomal monosomies. The differences were found between the cells with monosomies for different autosomes in the mechanisms of origin, intertissue localization, and phenotypic effects. It was shown that monosomies for chromosomes 7, 15, 21, and 22 in a mosaic state with the normal cell line can be compatible with the early stages of postimplantation differentiation of the cytotrophoblast. Predominant compartmentalization of the cells with monosomies for chromosomes 21 and 22 in the extraembryonic mesoderm, a derivative of epiblast, can be a critical factor, which makes the normal morphogenesis of embryonic structures impossible. [ABSTRACT FROM AUTHOR]

Karyotyping of noncultivated cells of 60 first-trimester spontaneous abortions (blighted ovum and missed abortions) was carried out using fluorescencein situ hybridization (FISH) with centromere-specific DNA probes for all chromosomes of the karyotype. Conventional cytogenetic study of these abortions was impossible because of cell culture failures. The algorithm is proposed for molecular cytogenetic FISH analysis of interphase karyotypes. Chromosome abnormalities were found in 32 fetuses (53.3%). In groups of missed abortions and blighted ovum, the frequency of numerical chromosome abnormalities was 50 and 60%, respectively. Both the numerical chromosome abnormalities typical of spontaneous human abortions (autosomal trisomies, sex chromosome aneuploidy, and polyploidy) and a relatively rare type of genomic imbalance unidentifiable by standard cytogenetic analysis (autosomal monosomies 7, 15, 21, and 22 in mosaic state) were observed. The frequency of these type of chromosome abnormalities comprised 19% of all known karyotype abnormalities determined in spontaneously aborted embryos. Note that the level of confined placental mosaicism in embryos with low cell proliferative activity was 25%, which is substantially higher than the corresponding parameter (1–2%) determined by prenatal diagnosis of chromosome abnormalities in developing embryos. The results of interphase FISH analysis of cells with low proliferative activity in vitro suggest that the pathology of early fetal development and missed abortion in humans are associated with a wider spectrum of chromosome abnormalities. [ABSTRACT FROM AUTHOR]

The review considers monogenic and chromosomal mutations associated with X-linked intellectual disability. Peculiarities of the development of the clinical phenotype in cases of different mutations were described. Special attention is paid to X-linked CNVs (microdeletions and microduplications). Chromosomal microaberrations most frequently found in patients with intellectual disability are presented. A modifying effect of X chromosome inactivation on the phenotype of carriers of X-linked mutations is discussed. The problems of interpretation of the clinical significance of X-linked CNVs are considered. [ABSTRACT FROM AUTHOR]

Properties of filtering-sorption materials based on basalt fibers and bentonite clays intended for the removal of oil products from water were studied. Optimal parameters of a feed providing the maximal purification efficiency with the minimal power consumption were determined. [ABSTRACT FROM AUTHOR]

The results of calculations and experimental determination of the neutronics characteristics of the IRT-T research reactor are presented. The IRT-T reactor is a pool reactor with rated thermal power 6 MW(t). The neutronics characteristics of the reactor were determined during the 2016–2017 runs. The calculations were performed using the precision software MCU-PTR with the MDBPT50 baseline nuclear constants. The experimental determination of the reactivity parameters was obtained by analyzing the current values of the reactor's standard control and protection system. Different approaches and methods for determining the efficiency of the reactor controls were considered. The calculations and experimental work were conducted in order to assess the effects of reactivity. [ABSTRACT FROM AUTHOR]

The level of chromosomal abnormalities in the somatic cells of adult individuals is characterized by significant interindividual variability, which may be partly affected by the genetic and epigenetic background. The epigenetic landscape in cells is largely determined by genome methylation. This study aimed to analyze the relationships between global genome methylation and the frequencies of chromosome abnormalities in lymphocytes of plutonium workers. The frequencies of chromosome aberrations, micronuclei, aneuploidy of chromosomes 2, 7, 8, 12, X, and Y and sister chromatid exchanges were analyzed in the lymphocytes of 40 male workers from a nuclear chemical facility (Seversk, Russia) with incorporated plutonium-239 and 49 healthy male volunteers who had no occupational exposure to ionizing radiation. The long interspersed nuclear elements-1 (LINE-1) methylation index was assessed as a well-known marker of global genome methylation. The frequencies of centromere-negative micronuclei (4.74 ± 2.26 vs. 3.02 ± 1.69‰), chromosome-type aberrations (0.81 ± 0.79 vs. 0.44 ± 0.69%), and total chromosome non-disjunction (0.93 ± 0.43 vs. 0.50 ± 0.25%) were significantly higher in the group of workers than in controls (p < 0.05). The LINE-1 methylation index did not differ significantly between the worker and control groups (74.93 ± 3.63 vs. 73.92 ± 4.62%). Correlations between LINE-1 methylation and the frequency of micronuclei (R = –0.35, p = 0.031) were observed in the control group, whereas correlations of LINE-1 methylation with chromatid-type aberrations (R = –0.42, p = 0.012) (but not chromosome-type aberrations) and with sister chromatid exchanges (R = –0.53, p = 0.004) were observed only in the group of plutonium workers. Thus, LINE-1 hypomethylation after plutonium exposure is associated mainly with chromatid breaks, either repaired or misrepaired. [ABSTRACT FROM AUTHOR]

An analysis of the prevalence of the CNTN6 gene microdeletions and microduplications in patients with neurodevelopmental disorders and healthy individuals was performed. Array comparative genomic hybridization and real-time PCR were used for screening of the CNTN6 gene copy number variations among 1070 patients with intellectual disability, 86 schizophrenia patients, and 200 healthy individuals. According to our current results and published data, the overall frequency of microdeletions and microduplications of the CNTN6 gene was estimated as 1 : 711 (0.14%) in patients with neurodevelopmental disorders and 1 : 917 (0.11%) in healthy individuals. CNTN6 microduplication in a control group was statistically significant in comparison with patient's group (p = 0.0372). For 43 out of 100 CNTN6 chromosomal mutations described in the literature, the inheritance from one of the parents was shown. In 12 cases out of 18 (67%), CNTN6 gene microdeletions and microduplications were inherited from a apparently healthy parent without phenotypic manifestations of the chromosomal mutation. [ABSTRACT FROM AUTHOR]

A method for identification of multiple transverse cracks and other localized defects in a rod by means of two spectra of longitudinal vibrations that correspond to free–free and fixed–free end conditions is presented. A numerical algorithm is developed that implements the method. The algorithm was tested on experimental data obtained on a cylindrical sample of aluminum alloy D16 with the created localized damages. The experiments were carried out on a rod with free ends. The created damages were ring grooves symmetrically located relative to the middle of the rod. With the help of such experiments, natural frequencies were obtained that correspond to two types of boundary conditions for a half-length rod. The experimental data were processed using the developed algorithm. The results showed that the model on which the developed algorithm is based describes well the longitudinal vibrations of the rod with localized damages in a fairly wide frequency range, and the algorithm enables to reconstruct multiple damages accurately enough. [ABSTRACT FROM AUTHOR]

Autoimmune hyperthyroidism (Graves' disease), which is caused by stimulating autoantibodies to the thyroid-stimulating hormone receptor (TSHR), and thyroid tumors, caused by a constitutively increased activity of this receptor, are widespread and have a poor prognosis. The drugs used to treat them are low effective and have many side effects. One of the therapeutic approaches to these thyroid diseases may be the use of TSH receptor allosteric regulators with an activity of inverse agonists. This work was aimed to study the effects of the compound TP48, previously synthesized in our laboratory, and a newly synthesized compound TPY5, with both of them referring to thieno[2,3-d]-pyrimidines, on basal and thyrotropin-releasing hormone (TRH)-stimulated levels of thyroid hormones (THs) in the rat blood and on the expression of genes responsible for TH synthesis in the rat thyroid gland. TP48 and TPY5 effectiveness was studied upon both intraperitoneal (20 mg/kg) and peroral (40 mg/kg) administration. Using ELISA, blood levels of free (fT4) and total (tT4) thyroxine, as well as free (fT3) and total (tT3) triiodothyronine, were assessed, including during stimulation with intranasal TRH (300 µg/kg). Gene expression for thyroid peroxidase (Tpo), thyroglobulin (Tg), Na+/I– symporter (Nis), type 2 deiodinase (Dio2), and TSH receptor (Tshr) in the thyroid gland was assessed by PCR. TPY5, administered via both routes, reduced both basal and TRH-stimulated plasma TH levels, while TP48 suppressed TH production only after intraperitoneal administration. Peroral TPY5 significantly reduced basal Tpo expression, as well as TRH-stimulated Tg and Dio2 expression. Intraperitoneal TP48 reduced only TRH-stimulated Tg and Dio2 expression. Quite surprisingly, peroral TPY5 and intraperitoneal TP48 reduced basal Tshr expression but did not prevent its inhibition by TRH. Thus, the novel compound TPY5 exhibits the activity of a TSH receptor inverse agonist and is effective when administered perorally, which is more in demand in medicine; it can be considered as a prototype of drugs to treat autoimmune hyperthyroidism and thyroid tumors. [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]

Miscarriage is potentially associated with abnormal epigenetic regulation of genes responsible for the development of the embryo and placenta. The aim of this work was to analyze the methylation level of various subfamilies of the LINE-1 retrotransposon, which makes up about 17% of the entire genome, in chorionic villi of spontaneous abortions of the first trimester of pregnancy with different karyotypes, including the most common aneuploidies. The methylation profile in the LINE-1 retrotransposon promoter was analyzed using targeted bisulfite massive parallel sequencing in chorionic villi of induced abortions (n = 39), spontaneous abortions with normal karyotype (n = 173), trisomy 16 (n = 62) and monosomy X (n = 46), and peripheral blood lymphocytes of healthy volunteers (n = 17). The level of methylation of the LINE-1 retrotransposon subfamilies in the control groups of adult lymphocytes and chorionic villi of induced abortions was the highest for evolutionarily young L1HS subfamilies, lower for the more ancient L1PA2 and L1PA3 subfamilies, and the lowest for the even more ancient L1PA4 subfamily. In the groups of spontaneous abortions, an increased level of LINE-1 methylation was observed, and this effect was more pronounced for the older LINE-1 subfamilies. The revealed patterns indicate less control over the older subfamilies of the LINE-1 retrotransposon in the human genome, which can potentially be used as regulatory elements for nearby genes involved in embryonic development. An increase in the level of methylation of such sequences can disrupt the development of the placenta and embryo and make a certain contribution to miscarriage. [ABSTRACT FROM AUTHOR]

Central precocious puberty (СPP) is caused by premature reactivation of the hypothalamic–pituitary–gonadal axis. Genetic, epigenetic, and environmental factors play a crucial role in determining the timing of puberty. In recent years, the KISS1, KISS1R, MKRN3, and DLK1 variants have been identified as hereditary causes of CPP. The MKRN3 and DLK1 genes are imprinted, and therefore epigenetic modifications that alter the expression of these genes are also considered as a cause of precocious puberty. With the progression of CPP, epigenetic factors such as DNA methylation, posttranslational modifications of histones and noncoding RNAs can mediate the relationship between the influence of genetic variants and the environment. CPP is also associated with other short- and long-term adverse health effects. This is the basis for research aimed at understanding the genetic and epigenetic causes of СPP. The purpose of this review is to summarize the published data on the molecular genetic and epigenetic mechanisms of the formation of СPP. [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]

A great amount of copy number variations (CNVs) are identified in the human genome. Most of them are neutral; nevertheless, the role of CNVs in the pathogenesis of hereditary diseases is still significant. Especially, this is important for neuropsychiatric disorders, such as intellectual disability and autism. When analyzing the CNV-associated diseases, the controversial question is to distinguish the pathogenic CNVs among common polymorphic variants and to predict the disease risk in other children of the family. Unfortunately, the mechanisms of phenotypic expression and incomplete penetrance of CNVs remain largely unknown. Currently, incomplete penetrance and variable expressivity of CNVs are attributed mainly to allelic interaction of different genetic variations. However, epigenetic mechanisms of gene expression regulation in the context of structural variation of the genome are poorly explored. It is possible that epigenetic modifications of the genome regions with CNVs may underlie the understanding of ways of phenotypic manifestations of structural variations in the human genome. [ABSTRACT FROM AUTHOR]

LINE-1 retrotransposon is the most common mobile genetic element in the genomes of various mammals, including humans. Its genes are represented by the greatest number of copies. For a long time, it has been considered that the presence of LINE-1 in genome reflects the limited ability of cells to eliminate it, and the retrotransposon activity is negative owing to the insertional mutagenesis. In recent years, the increased expression of LINE-1 retrotransposon and the activity of their encoded proteins observed in mammalian cells at different stages of development and, first of all, in early embryogenesis have been discussed in the literature. Is early embryogenesis the stage of development when the organism is more susceptible to the activity of retrotransposons, or does LINE-1 play some positive role in early embryonic development? This review is aimed at classifying the available data on the epigenetic regulation and the role of LINE-1 retrotransposon in embryogenesis of mammals. The link between the mechanisms of regulation of LINE-1 expression and the waves of epigenetic reprogramming is tracked in germ cells, during fertilization, and in blastocyst, as well as during the differentiation of embryonic and extraembryonic tissues. [ABSTRACT FROM AUTHOR]