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

Synapsis and recombination of autosomes and sex chromosomes in two terns (Sternidae, Charadriiformes, Aves)

The frequency of recombination and the patterns of crossover site distribution along the chromosomes vary considerably among animal species, including closely related species. Several hypotheses concerning the adaptive value and evolution of these variations were proposed. It was supposed that the recombination patterns of the species’ genomes are influenced by their phylogenetic history and ecology. However, most original data were obtained from mammals. The mammals show high karyological variability, which strongly influences the recombination patterns. Therefore it is important to study recombination rate and distribution in more karyologically stable taxa, such as reptiles and birds. We used immunolocalization of SYCP3, the protein of the lateral element of the synaptonemal complex (SC), centromere proteins and the mismatch-repair protein MLH1, which is associated with the recombination nodules, at the synaptonemal complex spreads of prophase oocytes of two tern species, black tern (Chlidonias niger) and common tern (Sterna hirundo). We first described the karyotype of Ch. niger (2n = 74, FN= 94) and identified suggestive rearrangements by which its karyotype differs from that of S. hirundo (2n = 68, FN = 90). We found that these species significantly differed by the numbers of the MLH1 foci per cell (Ch. niger: 53.0±4.2; S. hirundo: 44.1±5.0). We showed that the difference in the crossover numbers per cell was determined by the difference in the SC length (total and of individual bivalents) and by chromosomal rearrangements, which also influenced the distributions of crossover sites along the chromosomes. The difference in recombination patterns was higher between the rearranged homeologues than between the non-rearranged ones. We investigated the synaptic patterns of the heteromor phic Z and W chromosomes, localized the pseudoautosomal regions and estimated their lengths. In spite of several autosomal rearrangements, which differentiate these species, the structure and synaptic patterns of the sex chromosomes have not changed over 9 MY, which have passed since the moment of divergence between the genera Sterna and Chlidonias

Elements of mathematics in problems. Through olympiads and circles to profession

This is a collection of teaching materials used in several Russian universities, schools, and mathematical circles. Most problems are chosen in such a way that in the course of the solution and discussion a reader learns important mathematical ideas and theories. The materials can be used by pupils and students for self-study, and by teachers. This is an abridged pre-copyedit version of the published book submitted with the permission of the publisher. Each included individual material is self-contained and ready-for-use. Solutions to problems are not included intentionally. This collection consolidates updates of several arXiv submissions, e.g., arXiv:1305.2598.Comment: Edited by A. Skopenkov, M. Skopenkov, A. Zaslavsky. In Russian. Optimized for printing on A5 paper. Moscow Center for Continuous Mathematical Education, 2018, 592pp (in Russian

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

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

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

Отдаленные результаты консервативного лечения больных раком предстательной железы II—III стадии

The results of treatment of 170 patients with prostate cancer (T2—3N0—1M0—1) who received radiotherapy or radiotherapy plus antiandrogenic therapy from 1998 to 2003 were reviewed. The mean age was 69,5 year. The diagnosis was verified morphologically (Gl — 146 (85%), G2 — 10 (6%), G3 — 14 (8%) patients). The mean level of PSA was 24 ng/ml. Morphologic characteristics of tumors with defining of their differentiation grade according to Glisson scale were studied in 75 patients. Conformation radiotherapy with three dimensional planning was carried out by linear accelerator. Multipetal collimator was used for figured fields construction taking into account the spread of tumor.The total dose of radiation was 70—74 Gy. Only radiation therapy was carried out to 45 patients, whereas in 125 patients the radiotherapy was supplemented by administration of antiandrogenic therapy with Flucin or Zoladex. For initial assessment of tumor extent and evaluation of the treatment effect, we used transrectal ultrasound investigation (TRUSI) with ultrasonographic angiography. According to TRUSI, capsule invasion was found in 25 (16%) patients, which determines the risk of disease progression. Five year disease free survival in the absence of capsule invasion was 92%, whereas the capsule invasion diminishes it to 60%. With increasing levels of PSA long term results deteriorates: 5-year disease free survival was 80% at PSA level below 10 ng/ml, 72% at PSA level 10,1 — 20 ng/ml and 50% at PSA level higher than 20 ng/ml (p=0,36). Capsule invasion found on TRUSI and US angiography, high PSA level and Glisson sum are indications for administration of radiotherapy with antiandrogenic therapy. Unfavorable prognostic factors are found in one third patients over 70 years old, which demands employment of adequate antitumor treatment. Radiation therapy is an effective treatment for prostate cancer: 5-year observed survival was 86%, corrected survival — 91% and disease free survival — 78%

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