Recurrent triploidy due to a failure to complete maternal meiosis II: whole-exome sequencing reveals candidate variants.

Triploidy is a relatively common cause of miscarriage; however, recurrent triploidy has rarely been reported. A healthy 34-year-old woman was ascertained because of 18 consecutive miscarriages with triploidy found in all 5 karyotyped losses. Molecular results in a sixth loss were also consistent with triploidy. Genotyping of markers near the centromere on multiple chromosomes suggested that all six triploid conceptuses occurred as a result of failure to complete meiosis II (MII). The proband's mother had also experienced recurrent miscarriage, with a total of 18 miscarriages. Based on the hypothesis that an inherited autosomal-dominant maternal predisposition would explain the phenotype, whole-exome sequencing of the proband and her parents was undertaken to identify potential candidate variants. After filtering for quality and rarity, potentially damaging variants shared between the proband and her mother were identified in 47 genes. Variants in genes coding for proteins implicated in oocyte maturation, oocyte activation or polar body extrusion were then prioritized. Eight of the most promising candidate variants were confirmed by Sanger sequencing. These included a novel change in the PLCD4 gene, and a rare variant in the OSBPL5 gene, which have been implicated in oocyte activation upon fertilization and completion of MII. Several variants in genes coding proteins playing a role in oocyte maturation and early embryonic development were also identified. The genes identified may be candidates for the study in other women experiencing recurrent triploidy or recurrent IVF failure.

[Information theory of ageing: studying the effect of bone marrow transplantation on the life span of mice].

In this paper the method of life span extension of multicellular organisms (human) using the reservation of stem cells followed by autotransplantation has been proposed. As the efficiency of this method results from the information theory of ageing, it is important to verify it experimentally testing the basic concepts of the theory. Taking it into consideration, the experiment on the bone marrow transplantation to old mice from young closely-related donors of the inbred line was carried out. It has been shown, that transplanted animals exhibited a survival advantage, a mean life span increased by 34% as compared to the control. This result not only demonstrates the efficiency of the proposed method for life span extension of multicellular organisms, but also confirms the basis of the information theory of ageing.

[Use of fluorescence microspectral method for studying bone marrow EGFP+ cells transplantation in 5-fluorouracil-treated mice].

In this paper the experimental results of bone marrow transplantation from C57BL/6-Tg(ACTB-EGFP)1Osb/J transgenic mice into C57BL/6 mice subjected to 5-fluorouracil treatment are represented. It has been shown that EGFP+ cells engraftment in bone marrow, spleen and thymus of host mice after 5-Fu treatment significantly increased. More long-term engraftment was recorded after transplantation between closely related donors and 5-fluorouracil treatment hosts. We have also obtained data on differences in the dynamics of EGFP+ cells engraftment in host investigated organs. To assess the effect of the donor's bone marrow cells on the host immune system, functional activity of the synthetic apparatus (synthetic activity) of cells in bone marrow, spleen, thymus and blood have been investigated with fluorescence microspectral method. The results obtained allow of improving techniques for bone marrow transplantation without host irradiation in order to minimize the adverse effects.

[Comparative analysis of syngeneic and allogeneic transplantation without irradiation of the EGFP+ mice bone marrow cells with microspectral fluorescence method].

The experimental results on syngeneic and allogeneic transplantation of whole fraction of mice bone marrow cells without irradiation have been presented. Data on the dynamics of the donor cell colonization of bone marrow, spleen, thymus and blood of the recipient mice were obtained. The degree of immunogenicity of donor cells with syngeneic and allogeneic bone marrow transplantation based on the microspectral fluorescence method was evaluated. Within the framework of the experiment a low degree of immunogenicity of donor cells with syngeneic and allogeneic transplantation is shown. Importantly, allogeneic bone marrow transplantation did not cause any reduction in the mean life span of mice. These data and the results of our previous studies, demonstrating the mean life span increased by 34% with syngeneic transplantation in line C57BL/6 EGFP+, allow for developing different methods of cell therapy with no risk of fatal consequences of the immunological incompatibility between donor and recipient.

Maternal NLRP7 and C6orf221 variants are not a common risk factor for androgenetic moles, triploidy and recurrent miscarriage.

Maternal effect genes control early events of embryogenesis. Maternal homozygous and compound mutations in two such genes, NLRP7 and c6orf221, have been detected in the majority of women experiencing recurrent biparental hydatidiform moles. It was suggested that other forms of reproductive wastage, including diploid androgenetic moles, partial moles, polyploidy, recurrent spontaneous abortions and stillbirths of uncertain etiology, may be caused by NLRP7 or c6orf221 mutations in the mother. To elucidate which subpopulations of women with adverse reproductive outcomes should be screened for NLRP7/C6orf221 variants, we sequenced coding sequence and exon/intron boundaries of NLRP7 and C6orf221 in a well-defined group of 17 women with recurrent miscarriage and additional triploidy or complete hydatidiform moles. The major findings for this group were non-synonymous variants of NLRP7, rather than clearly pathogenic mutations. To assess the role of these variants, we genotyped them in a larger group including women with primary recurrent miscarriage (n = 39), paternal triploid conceptions (n = 22) and women with proven fertility after age 37 and no prior history of miscarriage or pregnancy complications (n = 52). No associations between non-synonymous NLRP7 variants and primary recurrent miscarriage or partial hydatidiform molar pregnancies were detected. Our findings suggest that neither mutations nor variants in NLRP7 and C6orf221 are major factors contributing to the risk of these types of pregnancy complications. Further studies in larger groups of patients and controls are needed to specify the impact of NLRP7 rare non-synonymous variants on genetic susceptibility to recurrent reproductive wastage.

[Study of radioprotective effect of "Soma" preparate].

Changes in the functional activity of the synthesis apparatus of rat blood lymphocytes under different scheme in application of bioadditive Soma after acute X-irradiation by fluorescent microspectrometry. Some metabolic indices in animals were investigated too. It has been shown the bioadditive Soma using in norm reliably increased the synthetic activity on days 13 and 20. Preliminary Soma using during a month followed by the same interval increased the animal radioresistance (scheme 1), while the Soma using immediately after irradiation (scheme 2) revealed no pronounced radioprotective effect. It was found the Soma increased metabolism that may be important to recover homeostasis. The results show the expediency of further investigation of the Soma radioprotective properties with different concentrations and schemes as well as the necessity of monitoring the immune system during Soma using.

Isolation and characterization of Escherichia coli strains producing microcins of B and C types.

A screening of 11956 enterobacteria isolates resulted in selection of seven active microcin-producing strains. The microcins were shown to be peptides or their derivatives with a rather broad spectrum of activity, mainly against Gram-negative bacteria. According to cross-immunity criteria, the microcins studied belonged to two of the previously suggested types, B (five strains) and C (two strains). Those of type B could be further classified into two subtypes on the account of differences in the spectrum of antibacterial activity. In five cases out of seven the microcin-producing ability has been attributed to plasmids that the strains harboured. The effect of microcins on sensitive cells was shown to depend on ompR and ompF gene products.

[Characterization of enterobacteria producing the broad-spectrum antibiotics microcins]. / Kharakteristika énterobakterii, produtsiruiushchikh antibiotiki shirokogo spektra deistviia mikrotsiny.

As a result of screening among 11956 enterobacteria strains isolated from feces of normal children, grown-ups and lambs, seven active microcin-producing strains were obtained. The microcins were shown to be peptides or their derivatives with a low molecular weight (less than 10,000) and a broad spectrum of activity, mainly against gram-negative bacteria. According to cross immunity criteria the microcins studied belonged to two different types. Those of type I could be further classified into two subtypes on the account of difference in the spectrum of antibacterial activity. In 5 cases out of 7 the microcin-producing ability and immunity to microcins have been attributed to plasmids that the strains harboured. The effect of microcins on sensitive cells depended on ompR and ompF gene products.