Olga Zinovieva

Bio: Olga Zinovieva is an academic researcher from Russian Academy of Sciences. The author has contributed to research in topics: Materials science & Deformation (meteorology). The author has an hindex of 9, co-authored 29 publications receiving 339 citations. Previous affiliations of Olga Zinovieva include Tomsk State University & Engelhardt Institute of Molecular Biology.

Altered expression of multiple genes involved in retinoic acid biosynthesis in human colorectal cancer.

Abstract: All-trans-retinoic acid (atRA), the oxidized form of vitamin A (retinol), regulates a wide variety of biological processes, such as cell proliferation and differentiation. Multiple alcohol, retinol and retinaldehyde dehydrogenases (ADHs, RDHs, RALDHs) as well as aldo-keto reductases (AKRs) catalyze atRA production. The reduced atRA biosynthesis has been observed in several human tumors, including colorectal cancer. However, subsets of atRA-synthesizing enzymes have not been determined in colorectal tumors. We investigated the expression patterns of genes involved in atRA biosynthesis in normal human colorectal tissues, primary carcinomas and cancer cell lines by RT-PCR. These genes were identified using transcriptomic data analysis (expressed sequence tags, RNA-sequencing, microarrays). Our results indicate that each step of the atRA biosynthesis pathway is dysregulated in colorectal cancer. Frequent and significant decreases in the mRNA levels of the ADH1B, ADH1C, RDHL, RDH5 and AKR1B10 genes were observed in a majority of colorectal carcinomas. The expression levels of the RALDH1 gene were reduced, and the expression levels of the cytochrome CYP26A1 gene increased. The human colon cancer cell lines showed a similar pattern of changes in the mRNA levels of these genes. A dramatic reduction in the expression of genes encoding the predominant retinol-oxidizing enzymes could impair atRA production. The most abundant of these genes, ADH1B and ADH1C, display decreased expression during progression from adenoma to early and more advanced stage of colorectal carcinomas. The diminished atRA biosynthesis may lead to alteration of cell growth and differentiation in the colon and rectum, thus contributing to the progression of colorectal cancer.

The computational micromechanics of materials with porous ceramic coatings

Abstract: Plastic strain localization and fracture in materials with porous coatings are investigated. A dynamic boundary-value problem is solved using a plane strain approximation. A microstructure-based numerical simulation is performed by the finite difference method. The microstructure of the coated material corresponds to that found experimentally and is assigned explicitly in the calculations. An initial finite difference mesh generation procedure for an explicit account of curvilinear pore-coating and coating-substrate interfaces is developed. Constitutive relations incorporate an elastoplastic model for the isotropic strain hardening of the steel substrate and a model for the brittle fracture of the coating. The specific character of the deformation and fracture is shown to be due to the local tension regions developing near pores and along the coating-substrate interface. Notably, the regions are formed both under tension and in compression of the coated material. The interrelation between inhomogeneous plastic flow in the steel substrate and crack propagation in the coating is examined.

A highly conserved eukaryotic protein family possessing properties of polypeptide chain release factor

Abstract: THE termination of protein synthesis in ribosomes is governed by termination (stop) codons in messenger RNAs and by polypeptide chain release factors (RFs). Although the primary structure of prokaryotic RFs and yeast mitochrondrial RF is established1–4, that of the only known eukaryotic RF (eRF)5 remains obscure. Here we report the assignment of a family of tightly related proteins (designated eRFl) from lower and higher eukaryotes which are structurally and functionally similar to rabbit eRF. Two of these proteins, one from human6 and the other from Xenopus laevis7 , have been expressed in yeast and Escherichia coli, respectively, purified and shown to be active in the in vitro RF assay. The other protein of this family, sup45 (supl) of Saccharomyces cerevisiae, is involved in omnipotent suppression during translation8–12. The amino-acid sequence of the eRFl family is highly conserved. We conclude that the eRFl proteins are directly implicated in the termination of translation in eukaryotes.

TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues.

Abstract: Genes showing higher expression in either tumor or metastatic tissues can help in better understanding tumor formation and can serve as biomarkers of progression or as potential therapy targets. Our goal was to establish an integrated database using available transcriptome-level datasets and to create a web platform which enables the mining of this database by comparing normal, tumor and metastatic data across all genes in real time. We utilized data generated by either gene arrays from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or RNA-seq from The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories. The altered expression within different platforms was analyzed separately. Statistical significance was computed using Mann–Whitney or Kruskal–Wallis tests. False Discovery Rate (FDR) was computed using the Benjamini–Hochberg method. The entire database contains 56,938 samples, including 33,520 samples from 3180 gene chip-based studies (453 metastatic, 29,376 tumorous and 3691 normal samples), 11,010 samples from TCGA (394 metastatic, 9886 tumorous and 730 normal), 1193 samples from TARGET (1 metastatic, 1180 tumorous and 12 normal) and 11,215 normal samples from GTEx. The most consistently upregulated genes across multiple tumor types were TOP2A (FC = 7.8), SPP1 (FC = 7.0) and CENPA (FC = 6.03), and the most consistently downregulated gene was ADH1B (FC = 0.15). Validation of differential expression using equally sized training and test sets confirmed the reliability of the database in breast, colon, and lung cancer at an FDR below 10%. The online analysis platform enables unrestricted mining of the database and is accessible at TNMplot.com.