DSpace Собрание: Scientific Reports is an open access journal publishing original research from across all areas of the natural sciences, psychology, medicine and engineering.

Complex biology of constitutional ring chromosomes structure and (in)stability revealed by somatic cell reprogramming

2021-02-22T00:00:00Z

Название: Complex biology of constitutional ring chromosomes structure and (in)stability revealed by somatic cell reprogramming Авторы: Nikitina, T. V.; Kashevarova, A. A.; Gridina, M. M.; Lopatkina, M. E.; Khabarova, A. A.; Yakovleva, Yu. S.; Menzorov, A. G.; Minina, Yu. A.; Pristyazhnyuk, I. E.; Vasilyev, S. A.; Fedotov, D. A.; Serov, O. L.; Lebedev, I. N. Краткий осмотр (реферат): Human ring chromosomes are often unstable during mitosis, and daughter cells can be partially or completely aneuploid. We studied the mitotic stability of four ring chromosomes, 8, 13, 18, and 22, in long-term cultures of skin fibroblasts and induced pluripotent stem cells (iPSCs) by GTG karyotyping and aCGH. Ring chromosome loss and secondary aberrations were observed in all fibroblast cultures except for r(18). We found monosomy, fragmentation, and translocation of indexed chromosomes. In iPSCs, aCGH revealed striking differences in mitotic stability both between iPSC lines with different rings and, in some cases, between cell lines with the same ring chromosome. We registered the spontaneous rescue of karyotype 46,XY,r(8) to 46,XY in all six iPSC lines through ring chromosome loss and intact homologue duplication with isoUPD(8)pat occurrence, as proven by SNP genotype distribution analysis. In iPSCs with other ring chromosomes, karyotype correction was not observed. Our results suggest that spontaneous correction of the karyotype with ring chromosomes in iPSCs is not universal and that pluripotency is compatible with a wide range of derivative karyotypes. We conclude that marked variability in the frequency of secondary rearrangements exists in both fibroblast and iPSC cultures, expanding the clinical significance of the constitutional ring chromosome.

Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression

2014-04-16T00:00:00Z

Название: Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression Авторы: Denisov, Evgeny V.; Litviakov, Nikolay V.; Zavyalova, Marina V.; Perelmuter, Vladimir M.; Vtorushin, Sergey V.; Tsyganov, Matvey M.; Gerashchenko, Tatiana S.; Garbukov, Evgeny Yu.; Slonimskaya, Elena M.; Cherdyntseva, Nadezhda V. Краткий осмотр (реферат): In this study, the influence of intratumoral morphological heterogeneity of breast cancer on neoadjuvant chemotherapy (NAC) efficiency was investigated. In particular, we analysed the association of NAC response and pre- and post-NAC expression of the main multidrug resistance (MDR) genes - ABCB1, ABCC1, ABCC5, ABCG1 and ABCG2, with the presence of different morphological structures in breast tumors. In addition, the expression of MDR genes was investigated in different morphological structures and in their microenvironment by comparing probes obtained using laser microdissection. The results of this study showed that tumors with alveolar structures were more frequently NAC-nonresponsive than cases without this structural type (p = 0.0028, Bonferroni-corrected p = 0.014). The presence of trabecular structures in breast tumors was also associated with chemoresistance (p = 0.0272, Bonferroni-corrected p = 0.136). High expression of MDR genes was not found in alveolar structures (including their microenvironment) and in tumors containing this structural type. In contrast, more active MDR genes and expression of the ABCB1 gene were found only in trabecular structures. Taken together, our data indicate that breast tumors with alveolar structures possess resistance to NAC, which is not related to high expression of MDR genes, whereas chemoresistance of tumors with trabecular structures can depend on the expression level of ABCB1.

Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model

2017-04-24T00:00:00Z

Название: Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model Авторы: Khodanovich, Marina Yu; Sorokina, Irina V.; Glazacheva, Valentina Yu; Akulov, Andrey E.; Nemirovich-Danchenko, Nikolay M.; Romashchenko, Alexander V.; Tolstikova, Tatyana G.; Mustafina, Lilia R.; Yarnykh, Vasily L. Краткий осмотр (реферат): Cuprizone-induced demyelination in mice is a frequently used model in preclinical multiple sclerosis research. A recent quantitative clinically-targeted MRI method, fast macromolecular proton fraction (MPF) mapping demonstrated a promise as a myelin biomarker in human and animal studies with a particular advantage of sensitivity to both white matter (WM) and gray matter (GM) demyelination. This study aimed to histologically validate the capability of MPF mapping to quantify myelin loss in brain tissues using the cuprizone demyelination model. Whole-brain MPF maps were obtained in vivo on an 11.7T animal MRI scanner from 7 cuprizone-treated and 7 control С57BL/6 mice using the fast single-point synthetic-reference method. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. Significant (p < 0.05) demyelination in cuprizone-treated animals was found according to both LFB staining and MPF in all anatomical structures (corpus callosum, anterior commissure, internal capsule, thalamus, caudoputamen, and cortex). MPF strongly correlated with quantitative histology in all animals (r = 0.95, p < 0.001) as well as in treatment and control groups taken separately (r = 0.96, p = 0.002 and r = 0.93, p = 0.007, respectively). Close agreement between histological myelin staining and MPF suggests that fast MPF mapping enables robust and accurate quantitative assessment of demyelination in both WM and GM.