Polymorphism rs3088232 in the BRDT gene is associated with idiopathic male infertility in the West Siberian Region of Russia

Allelic variants of genes involved in spermatogenesis can contribute to the genetic predisposition to idiopathic male infertility. In the present study we investigated the association of polymorphism rs3088232 in the BRDT gene with the risk of this pathology on the sample of 105 infertile patients and 230 healthy controls. We revealed the association of allele G (OR = 1.80; CI 1.16—2.80; p = 0.008) and genotype GG (OR = 6.47; CI 1.23—34.15; p = 0.01) with idiopathic male infertility

Germline-restricted chromosome (GRC) is widespread among songbirds

An unusual supernumerary chromosome has been reported for two related avian species, the zebra and Bengalese finches. This large, germline-restricted chromosome (GRC) is eliminated from somatic cells and spermatids and transmitted via oocytes only. Its origin, distribution among avian lineages, and function were mostly unknown so far. Using immunolocalization of key meiotic proteins, we found that GRCs of varying size and genetic content are present in all 16 songbird species investigated and absent from germline genomes of all eight examined bird species from other avian orders. Results of fluorescent in situ hybridization of microdissected GRC probes and their sequencing indicate that GRCs show little homology between songbird species and contain a variety of repetitive elements and unique sequences with paralogs in the somatic genome. Our data suggest that the GRC evolved in the common ancestor of all songbirds and underwent significant changes in the extant descendant lineages

Negative heterosis for meiotic recombination rate in spermatocytes of the domestic chicken Gallus gallus

Benefits and costs of meiotic recombination are a matter of discussion. Because recombination breaks allele combinations already tested by natural selection and generates new ones of unpredictable fitness, a high recombination rate is generally beneficial for the populations living in a fluctuating or a rapidly changing environment and costly in a stable environment. Besides genetic benefits and costs, there are cytological effects of recombination, both positive and negative. Recombination is necessary for chromosome synapsis and segregation. However, it involves a massive generation of double-strand DNA breaks, erroneous repair of which may lead to germ cell death or various mutations and chromosome rearrangements. Thus, the benefits of recombination (generation of new allele combinations) would prevail over its costs (occurrence of deleterious mutations) as long as the population remains sufficiently heterogeneous. Using immunolocalization of MLH1, a mismatch repair protein, at the synaptonemal complexes, we examined the number and distribution of recombination nodules in spermatocytes of two chicken breeds with high (Pervomai) and low (Russian Crested) recombination rates and their F1 hybrids and backcrosses. We detected negative heterosis for recombination rate in the F1 hybrids. Backcrosses to the Pervomai breed were rather homogenous and showed an intermediate recombination rate. The differences in overall recombination rate between the breeds, hybrids and backcrosses were mainly determined by the differences in the crossing over number in the seven largest macrochromosomes. The decrease in recombination rate in F1 is probably determined by difficulties in homology matching between the DNA sequences of genetically divergent breeds. The suppression of recombination in the hybrids may impede gene flow between parapatric populations and therefore accelerate their genetic divergence

Ribosomal DNA as DAMPs Signal for MCF7 Cancer Cells

Introduction: The cell free ribosomal DNA (cf-rDNA) is accrued in the total pool of cell free DNA (cfDNA) in some non-cancer diseases and demonstrates DAMPs characteristics. The major research questions: (1) How does cell free rDNA content change in breast cancer; (2) What type of response in the MCF7 breast cancer cells is caused by cf-rDNA; and (3) What type of DNA sensors (TLR9 or AIM2) is stimulated in MCF7 in response to the action of cf-rDNA?Materials and Methods: CfDNA and gDNA were isolated from the blood plasma and the cells derived from 38 breast cancer patients and 20 healthy female controls. The rDNA content in DNA was determined using non-radioactive quantitative hybridization. In order to explore the rDNA influence on MCF7 breast cancer cells, the model constructs (GC-DNAs) were applied: pBR322-rDNA plasmid (rDNA inset 5836 bp long) and pBR322 vector. ROS generation, DNA damage, cell cycle, expression of TLR9, AIM2, NF-kB, STAT3, and RNA for 44 genes affecting the cancer cell viability were evaluated. The methods used: RT-qPCR, fluorescent microscopy, immunoassay, flow cytometry, and siRNA technology.Results: The ratio R = cf-rDNA/g-rDNA for the cases was higher than for the controls (median 3.4 vs. 0.8, p < 10−8). In MCF7, GC-DNAs induce a ROS burst, DNA damage response, and augmentation of NF-kB and STAT3 activity. The number of the apoptotic cells decreases, while the number of cells with an instable genome (G2/M– arrest, micronuclei) increase. Expression of anti-apoptotic genes (BCL2, BCL2A1, BCL2L1, BIRC3, MDM2) is elevated, while expression of pro-apoptotic genes (BAX, BID, BAD, PMAIP1, BBC3) is lowered. The cells response for pBR322-rDNA is much more intense and develops much faster, than response for pBR322, and is realized through activation of TLR9- MyD88 - NF-kB- signaling. This difference in response speed is owing to the heightened oxidability of pBR322-rDNA and better ability to penetrate the cell. Induction of TLR9 expression in MCF7 is followed by blocking AIM2 expression.Conclusion: (1) Ribosomal DNA accumulates in cfDNA of breast cancer patients; (2) Cell free rDNA induce DNA damage response and stimulates cells survival, including cells with an instable genome; (3) Cell free rDNA triggers TLR9- MyD88- NF-kB- signaling, with significantly repressing the expression of AIM2

Low-Dose Ionizing Radiation Affects Mesenchymal Stem Cells via Extracellular Oxidized Cell-Free DNA: A Possible Mediator of Bystander Effect and Adaptive Response

We have hypothesized that the adaptive response to low doses of ionizing radiation (IR) is mediated by oxidized cell-free DNA (cfDNA) fragments. Here, we summarize our experimental evidence for this model. Studies involving measurements of ROS, expression of the NOX (superoxide radical production), induction of apoptosis and DNA double-strand breaks, antiapoptotic gene expression and cell cycle inhibition confirm this hypothesis. We have demonstrated that treatment of mesenchymal stem cells (MSCs) with low doses of IR (10 cGy) leads to cell death of part of cell population and release of oxidized cfDNA. cfDNA has the ability to penetrate into the cytoplasm of other cells. Oxidized cfDNA, like low doses of IR, induces oxidative stress, ROS production, ROS-induced oxidative modifications of nuclear DNA, DNA breaks, arrest of the cell cycle, activation of DNA reparation and antioxidant response, and inhibition of apoptosis. The MSCs pretreated with low dose of irradiation or oxidized cfDNA were equally effective in induction of adaptive response to challenge further dose of radiation. Our studies suggest that oxidized cfDNA is a signaling molecule in the stress signaling that mediates radiation-induced bystander effects and that it is an important component of the development of radioadaptive responses to low doses of IR

ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ ТРАНСПЛАНТАЦИИ ТРУПНОЙ ПЕЧЕНИ

Aim of the study was to evaluate patient and graft survival after liver transplantation (LT) and to determine if primary disease diagnosis, early graft dysfunction or other factors affect it. Furthermore, we analyzed the reasonsof short-term and long-term deaths or retransplantations.Materials and methods. 192 LTs from donors with brain death were performed from December 2004 until June 2014. Recipient age varied from 5 to 71 years. Most frequent diagnosis was liver cirrhosis (mainly due to hepatitis C), then hepatocellular carcinoma (HCC), liver graft dysfunction, etc.Results and discussion. 1-year patient survival is 89.5%, graft survival is 87.7%, 3-year –87% and 84.6%, respectively, and 5-year – 83.5% and 83.0%, respectively. Early mortality (in fi rst 30 days after transplantation) was 8%, long-term mortality – 5.9%. Primary non-function graft (PNF) was the reason of 66.7% early deaths. In the long term, infections and oncology were the reasons of death with the same frequency – 36.4%. Early graft dysfunction including primary non-function signifi cantly decreases short term survival (p = 0.0002). Nevertheless, in the majority of cases graft function improves and doesn’t affect survival. Donor factors play role in outcomes: early dysfunction is higher (40.6%) in extended criteria donor group than in standard donor group (р = 0.0431). PNF has the same trend – 8.5% and 0.0%, respectively, but without signifi cance (р =0.0835). 5-year survival is remarkably lower in HCC group 40.8% (p = 0.003) than in other groups.Conclusion: survival after liver transplantation in our Center is comparable with the results of the world’s centers.Цель данного исследования – изучить выживаемость больных и трансплантатов в зависимости от диагно-за первичного заболевания, наличия ранней дисфункции трансплантата, причины летальности на разныхсроках, проанализировать результаты ретрансплантаций.Материалы и методы. С декабря 2004 года по июнь 2014 года в ФНЦТИО было выполнено 192 трансплантации печени от доноров с диагнозом «смерть мозга» 186 реципиентам в возрасте от 5 лет до 71 года. В структуре показаний к трансплантации на первом месте по частоте находился цирроз печени, чаще всего в исходе гепатита С, затем гепатоцеллюлярная карцинома, дисфункция трансплантата печени и другие заболевания.Результаты и обсуждение. Однолетняя выживаемость реципиентов составляет 89,5%, трансплантатов – 87,7%, трехлетняя – 87 и 84,6%, пятилетняя – 83,5 и 83,0% соответственно. Периоперационная летальность составила 8%, отдаленная – 5,9%. Основной причиной смерти в раннем послеоперационном периоде являлись первично не функционирующие трансплантаты (ПНФТ) – 66,7% потерь, в отдаленном – одинаково часто (36,4% потерь) злокачественные новообразования и инфекции. Ранняя дисфункция трансплантата (РДТ), включая ПНФТ, статистически значимо снижает выживаемость в раннем послеоперационном периоде (p = 0,0002). Однако у большинства больных РДТ обратима и в этом случае в дальнейшем не влияет на выживаемость. При использовании трансплантата от стандартного донора частота РДТ была статистически значимо меньше – 21,2%, чем при расширении критериев – 40,6% (р = 0,0431), а частота ПНФТ составила 0,0 и 8,5%, соответственно (р = 0,0835). Пятилетняя выживаемость при трансплантации по поводу ГЦК значимо ниже, чем при наличии других показаний – 40,8% (p = 0,003).Заключение: выживаемость реципиентов после трансплантации печени в нашем центре на сроке до 10 лет сопоставима с результатами мировых регистров

Organic chemistry. History and mutual relations of universities of Russia

© 2017, Pleiades Publishing, Ltd. The review describes the history of development of organic chemistry in higher schools of Russia over a period of 170 years, since the emergence of organic chemistry in our country till now