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The aim is to conduct a cardiometric assessment of formation of acute and late toxic disorders in experimental animals with Guerin's carcinoma during carboplatin chemotherapy against the background of L-carnitine medication. Materials and methods The study was performed using 43 white outbred male rats weighing 200-230 g, 16 of them intact (without a tumor) and 27 with inoculated Guerin's carcinoma, who were administered chemotherapy drug Carboplatin-Teva (CP) intraperitoneally at a dose of 50 mg/kg of body weight twice at an interval of 5 days. L-carnitine was administered per os using a gastric tube in an amount of 0.3 ml of the solution. ECG was recorded using hemodynamic PC-assisted analyzer CARDIOCODE (ST LLC CAR-DIOCODE, Taganrog, Russia) in anesthesia-free animals fixed onto the operating table in the back position. The recording was performed for 15 seconds with skin surface mini-electrodes. Results 24 hours after the administration of carboplatin to intact ani-mals and tumor-bearing rats, early symptoms of cardiotoxicity appeared in the form of an initial P-wave response as a marker of an increase in the load on the atria and a slowdown in its pumping function. The further delayed effect of carboplatin demonstrated the smoothing of the P wave on the ECG, which indicated a stable effect of increasing the tonus of the atrial walls. A pronounced sign of cardiomyopathy was a decrease in the amplitude of the QR phase and an attenuation of QRS, reflecting a decrease in the energetic potential of cardiomyo-cytes. The corrective effect of L-carnitine in animals with tumor chemotherapy was manifested in the restoration of the P wave duration to the initial level of 0.019 s, and the duration of the PQ and QRS intervals began to correspond to intact animals without cytostatic administration, 0.03 s and 0.09 s, respectively. That was an evidence for the effect of the cardioprotector on the supression of the carboplatin toxic action. Conclusions Studies with the use of the model of malignant tumor growth and antitumor therapy with carboplatin indicate that there are manifestations of early and late symptoms of cardiotoxicity in the form of pathological shifts in some ECG phase constants. The possibility of correcting disorders can be provided by cardioprotector L-carnitine as a participant in the energy supply to the cardiac mitochondria.

A sediment column of 155 cm in length was retrieved by hammer corer in the deepest central part of lake Shira. Solid samples were prepared from the wet cores by freeze drying and impregnating with epoxy resin. The inter annual and inter seasonal variations in the trace element composition of annual layers are studied by means of X-ray scanning microanalysis with synchrotron radiation on the VEPP-3 and BESSY-II storage rings. Detailed experimental investigations of the internal structure of annual layers allowed the authors to create a lithological-geochemical model of sedimentation in Lake Shira, and to find climatically correlated minor elements. This model of the annual cycle of sedimentation was used to explain the periodic white layers with high Sr contents in the core. Thick 3 cm-5 cm light carbonate Sr-enriched intervals correspond to an extremely low level of the lake and are repeated every 450-550 years.

Reconstruction of climate change in Central Asia over the last millennium with an annual resolution was made using geochemical and biological proxy in lake bottom sediments and tree-ring data. We investigated the lake in Central Asia- Teletskoe (Altai), Kucherla (Altai), Baikal, Arahlei (Chita) - and adjacent areas. Cores of bottom sediments were investigated by method of scanning X-ray fluorescent analysis with synchrotron radiation with the spatial resolution of 0.1 mm. It corresponds to the time resolution ~ 0.2-0.5 year. At each point analyzed more than 30 trace elements from K to U. Geochemical proxy of terrigenous, organogenous and aerosol components of sediments well correlated with regional meteodata for the last 100-150 years. Time series of lithological-geochemical indicators of climate change based on dating by 14C, 137Cs and 210Pb was calibrated by instrumental hydrometeorological data. We used tree-ring series together with element contents as an additional proxy for calculation of transfer function, considering that tree-ring series are response to summer temperature in this climatic zone. Annual temperature and precipitation change for the Central Asia region (0 - 1000 years ago) have been reconstructed using the transfer functions such as: time series proxy=function (temperature, precipitation).

Chemicals reactivating epigenetically silenced genes target diverse classes of enzymes, including DNMTs, HDACs, HMTs and BET protein family members. They can strongly influence the expression of genes and endogenous retroviral elements with concomitant dsRNA synthesis and massive transcription of LTRs. Chemicals reactivating gene expression may cause both beneficial effects in cancer cells and may be hazardous by promoting carcinogenesis. Among chemicals used in medicine and commerce, only a small fraction has been studied with respect to their influence on epigenetic silencing. Screening of chemicals reactivating silent genes requires adequate systems mimicking whole-genome processes. We used a HeLa TSA-inducible cell population (HeLa TI cells) obtained by retroviral infection of a GFP -containing vector followed by several rounds of cell sorting for screening purposes. Previously, the details of GFP epigenetic silencing in HeLa TI cells were thoroughly described. Herein, we show that the epigenetically repressed gene GFP is reactivated by 15 agents, including HDAC inhibitors–vorinostat, sodium butyrate, valproic acid, depsipeptide, pomiferin, and entinostat; DNMT inhibitors–decitabine, 5-azacytidine, RG108; HMT inhibitors–UNC0638, BIX01294, DZNep; a chromatin remodeler–curaxin CBL0137; and BET inhibitors–JQ-1 and JQ-35. We demonstrate that combinations of epigenetic modulators caused a significant increase in cell number with reactivated GFP compared to the individual effects of each agent. HeLa TI cells are competent to metabolize xenobiotics and possess constitutively expressed and inducible cytochrome P450 mono-oxygenases involved in xenobiotic biotransformation. Thus, HeLa TI cells may be used as an adequate test system for the extensive screening of chemicals, including those that must be metabolically activated. Studying the additional metabolic activation of xenobiotics, we surprisingly found that the rat liver S9 fraction, which has been widely used for xenobiotic activation in genotoxicity tests, reactivated epigenetically silenced genes. Applying the HeLa TI system, we show that N-nitrosodiphenylamine and N-nitrosodimethylamine reactivate epigenetically silenced genes, probably by affecting DNA methylation.

Background There are many reports on rearrangements occurring separately in the regions of chromosomes 9p and 15q affected in the case under study. 15q duplication syndrome is caused by the presence of at least one extra maternally derived copy of the Prader–Willi/Angelman critical region. Trisomy 9p is the fourth most frequent chromosome anomaly with a clinically recognizable syndrome often accompanied by intellectual disability. Here we report a new case of a patient with maternally derived unique complex sSMC resulting in partial trisomy of both chromosomes 9 and 15 associated with intellectual disability. Case presentation We characterise a supernumerary derivative chromosome 15: 47,XY,+der(15)t(9;15)(p21.2;q13.2), likely resulting from 3:1 malsegregation during maternal gametogenesis. Chromosomal analysis showed that a phenotypically normal mother is a carrier of balanced translocation t(9;15)(p21.1;q13.2). Her 7-year-old son showed signs of intellectual disability and a number of physical abnormalities including bilateral cryptorchidism and congenital megaureter. The child’s magnetic resonance imaging showed changes in brain volume and in structural and functional connectivity revealing phenotypic changes caused by the presence of the extra chromosome material, whereas the mother’s brain MRI was normal. Sequence analyses of the microdissected der(15) chromosome detected two breakpoint regions: HSA9:25,928,021-26,157,441 (9p21.2 band) and HSA15:30,552,104-30,765,905 (15q13.2 band). The breakpoint region on chromosome HSA9 is poor in genetic features with several areas of high homology with the breakpoint region on chromosome 15. The breakpoint region on HSA15 is located in the area of a large segmental duplication. Conclusions We discuss the case of these phenotypic and brain MRI features in light of reported signatures for 9p partial trisomy and 15 duplication syndromes and analyze how the genomic characteristics of the found breakpoint regions have contributed to the origin of the derivative chromosome. We recommend MRI for all patients with a developmental delay, especially in cases with identified rearrangements, to accumulate more information on brain phenotypes related to chromosomal syndromes.

Dairy goat breeding is a new developing branch of animal husbandry in Russia. The prospects for processing goat’s milk are very wide, which is due to an increase in consumer demand for it. Obtaining the maximum amount of products and maintaining animal health is possible with the use of modern feed products. Therefore, an important and urgent task of scientific research is to study the productivity of dairy goats when feeding dry biomass of microalgae Chlorella Vulgaris, which was the purpose of this work. The objects of the study were dairy goats in the type of Zaanen breed. To conduct an experiment based on the principle of groups of analogues, taking into account live weight and age, four groups of female goats (three experimental and one control) of 20 animals each (according to the Ovsyannikov method) were formed. The animals of the control group received the basic household ration, and dry biomass of Chlorella Vulgaris microalgae was introduced into the diet of the experimental groups in doses of 4; 6; 8 g / kg of body weight / day. As a result of the experiment, it was found that the introduction of an experimental drug into the diet of goats increased the average daily milk yield of goats of the first experimental group by 0.02%, the second experimental group by 1.66 and the third experimental group by 3.27%, which allows us to determine the most optimal dose of the introduction of an experimental probiotic drug into the diet of goats, which amounted to 6 g / kg of body weight.

The presence of small supernumerary marker chromosomes (sSMCs) in a karyotype leads to diagnostic questions because the resulting extra material may cause abnormal development depending on the origin of the duplication/triplication. Because SMCs are so small, their origin cannot be determined by conventional cytogenetic techniques, and new molecular cytogenetic methods are necessary. Here, we applied a target approach to chromosome rearrangement analysis by isolating a chromosome of interest via microdissection and using it in fluorescence in situ hybridization (FISH) as a probe in combination with whole-chromosome painting probes. This approach allows to identify origins of both the euchromatin and repeat-rich regions of a marker. We propose to use whole-chromosome libraries and microdissected chromosomes in FISH to identify SMCs enriched with repeated sequences. We show that the methodology is successful in identifying the composition of a satellited marker chromosome.

The Robertsonian translocations inherited from parents with a normal phenotype are often discovered through children with pathogenesis. The exact causes of pathologies in children with clinical manifestations are often unknown and vary greatly in the reported cases: uniparental disomy, de novo rearrangements, changes in methylation patterns and gene expression, including ribosomal genes. Molecular-cytogenetic investigation of a clinical case of intellectual disability. GTG-banding, Ag-NOR staining, fluorescent in situ hybridization, PCR, real-time PCR. We describe a family case of a translocation rob (13; 14) and elevated rRNA expression in the proband with developmental delay and in his phenotypically normal mother. We show the loss of the p-arms of original chromosomes and the absence of NORs on the derived chromosome. The whole-chromosome uniparental disomy is excluded. The translocated chromosome in the proband was most likely inherited from the mother and did not come about de novo with normal chromosomes 13 and 14 being obtained from the father. The cause of the pathogenesis in the proband still remains unknown. We hypothesize that it could be caused by impaired imprinting manifesting in altered methylation levels of loci on the derivative chromosome.

Background Small supernumerary marker chromosomes can be derived from autosomes and sex chromosomes and can accompany chromosome pathologies, such as Turner syndrome. Case presentation Here, we present a case report of a patient with mosaic Turner syndrome and Dandy-Walker syndrome carrying a marker chromosome. We showed the presence of the marker chromosome in 33.8% of blood cells. FISH of the probe derived from the marker chromosome by microdissection revealed that it originated from the centromeric region of chromosome X. Additionally, we showed no telomeric sequences and no XIST sequence in the marker chromosome. This is the first report of these two syndromes accompanied by the presence of a marker chromosome. Conclusion Marker chromosome was X-derived and originated from centromeric region. Patient has mild symptoms but there is no XIST gene in marker chromosome. Trial registration CPG137 . Registered 03 March 2017.

Intellectual disability (ID) is an important medical and social problem that can be caused by different genetic and environmental factors. One such factor could be rDNA amplification and changes in rRNA expression and maturation. The aim of the present study was to investigate rRNA levels in patients with heteromorphism of the p-arms of acrocentric chromosomes bearing nucleolus organizer regions compared to a healthy control group. Frequencies of p-arms enlargements in patients with ID and in healthy people were analyzed by G-banding screening. rRNA gene copy numbers on affected acrocentric chromosomes in peripheral blood lymphocytes were evaluated in ID patients and healthy bearers using FISH, and in immortalized lymphocytes of one patient – using FISH and real time PCR. Simultaneously, levels of 18S, 28S and 5,8S rRNA in both groups by means of qRT-PCR were investigated. No difference in acrocentric chromosome heteromorphism frequency in patients versus the healthy group were found. However, we found an amplification of rDNA, a significant elevation in 28S and 5.8S rRNA expression and changes in the 28S/18S rRNA ratio in ID patients compared to healthy controls. At the same time, FISH appeared to be not reliable enough for copy number evaluation, but RT-PCR showed rDNA copy changes in heteromorphic cells compared to normal. Our findings indicate a loss of the correct regulation of rDNA activity and processing after amplification. This could disturb the ribosomal apparatus and thus lead to intellectual disability via at least two mechanisms.