Patrocles: a database of polymorphic miRNA-mediated gene regulation in vertebrates

The Patrocles database (http://www.patrocles.org/) compiles DNA sequence polymorphisms (DSPs) that are predicted to perturb miRNA-mediated gene regulation. Distinctive features include: (i) the coverage of seven vertebrate species in its present release, aiming for more when information becomes available, (ii) the coverage of the three compartments involved in the silencing process (i.e. targets, miRNA precursors and silencing machinery), (iii) contextual information that enables users to prioritize candidate ‘Patrocles DSPs’, including graphical information on miRNA-target coexpression and eQTL effect of genotype on target expression levels, (iv) the inclusion of Copy Number Variants and eQTL information that affect miRNA precursors as well as genes encoding components of the silencing machinery and (v) a tool (Patrocles finder) that allows the user to determine whether her favorite DSP may perturb miRNA-mediated gene regulation of custom target sequences. To support the biological relevance of Patrocles' content, we searched for signatures of selection acting on ‘Patrocles single nucleotide polymorphisms (pSNPs)’ in human and mice. As expected, we found a strong signature of purifying selection against not only SNPs that destroy conserved target sites but also against SNPs that create novel, illegitimate target sites, which is reminiscent of the Texel mutation in sheep

Composition of Conditioned Media from Radioresistant and Chemoresistant Cancer Cells Reveals miRNA and Other Secretory Factors Implicated in the Development of Resistance

Resistance to chemo- or radiotherapy is the main obstacle to consistent treatment outcomes in oncology patients. A deeper understanding of the mechanisms driving the development of resistance is required. This review focuses on secretory factors derived from chemo- and radioresistant cancer cells, cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), and cancer stem cells (CSCs) that mediate the development of resistance in unexposed cells. The first line of evidence considers the experiments with conditioned media (CM) from chemo- and radioresistant cells, CAFs, MSCs, and CSCs that elevate resistance upon the ionizing radiation or anti-cancer drug exposure of previously untreated cells. The composition of CM revealed factors such as circular RNAs; interleukins; plasminogen activator inhibitor; and oncosome-shuttled lncRNAs, mRNAs, and miRNAs that aid in cellular communication and transmit signals inducing the chemo- and radioresistance of sensitive cancer cells. Data, demonstrating that radioresistant cancer cells become resistant to anti-neoplastic drug exposure and vice versa, are also discussed. The mechanisms driving the development of cross-resistance between chemotherapy and radiotherapy are highlighted. The secretion of resistance-mediating factors to intercellular fluid and blood brings attention to its diagnostic potential. Highly stable serum miRNA candidates were proposed by several studies as prognostic markers of radioresistance; however, clinical studies are needed to validate their utility. The ability to predict a treatment response with the help of the miRNA resistance status database will help with the selection of an effective therapeutic strategy. The possibility of miRNA-based therapy is currently being investigated with ongoing clinical studies, and such approaches can be used to alleviate resistance in oncology patients

Structural and Spectroscopic Features of the Bixbyite-Type Yttrium Scandate Doped by Rare-Earth Ions

Yttrium scandate crystal fiber has been obtained through laser-heated pedestal growth. The crystal belongs to a bixbyite crystal structure and crystallizes in Ia3¯ space group. X-ray diffraction method shows a lattice parameter of a = 10.228(1) Å. Factor-group analysis of YScO3 Raman spectra points to high degree of disorder in crystal structure of the new compound. Spectral-kinetic investigation of the crystal fibers doped by rare-earth ions points to the presence of two independent active optical centers of rare-earth ions. Moreover, the character of rare-earth impurities’ distribution is independent on a rare-earth ionic radius size

Structural and Spectroscopic Features of the Bixbyite-Type Yttrium Scandate Doped by Rare-Earth Ions

Yttrium scandate crystal fiber has been obtained through laser-heated pedestal growth. The crystal belongs to a bixbyite crystal structure and crystallizes in Ia3¯ space group. X-ray diffraction method shows a lattice parameter of a = 10.228(1) Å. Factor-group analysis of YScO3 Raman spectra points to high degree of disorder in crystal structure of the new compound. Spectral-kinetic investigation of the crystal fibers doped by rare-earth ions points to the presence of two independent active optical centers of rare-earth ions. Moreover, the character of rare-earth impurities’ distribution is independent on a rare-earth ionic radius size

Changes in the Number of Double-Strand DNA Breaks in Chinese Hamster V79 Cells Exposed to γ-Radiation with Different Dose Rates

A comparative investigation of the induction of double-strand DNA breaks (DSBs) in the Chinese hamster V79 cells by γ-radiation at dose rates of 1, 10 and 400 mGy/min (doses ranged from 0.36 to 4.32 Gy) was performed. The acute radiation exposure at a dose rate of 400 mGy/min resulted in the linear dose-dependent increase of the γ-H2AX foci formation. The dose-response curve for the acute exposure was well described by a linear function y = 1.22 + 19.7x, where “y” is an average number of γ-H2AX foci per a cell and “x” is the absorbed dose (Gy). The dose rate reduction down to 10 mGy/min lead to a decreased number of γ-H2AX foci, as well as to a change of the dose-response relationship. Thus, the foci number up to 1.44 Gy increased and reached the “plateau” area between 1.44 and 4.32 Gy. There was only a slight increase of the γ-H2AX foci number (up to 7) in cells after the protracted exposure (up to 72 h) to ionizing radiation at a dose rate of 1 mGy/min. Similar effects of the varying dose rates were obtained when DNA damage was assessed using the comet assay. In general, our results show that the reduction of the radiation dose rate resulted in a significant decrease of DSBs per cell per an absorbed dose