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The process of domestication is associated with decrease in effective population size, which in turn leads to accumulation of slightly-deleterious mutations due to genetic drift. To maintain genome quality at a high level, we propose to use a stress-induced strong purifying selection, which based on negative epistasis, can effectively eliminate organisms with an excess of deleterious variants. Here, to identify stress factors, which interact with the effect of deleterious mutations we performed a proof-of-principle experiment with several regimes of a heat shock. We observed that fitness of mutated versus wild-type carp lines drops stronger after heat shock, which is a signature of a negative epistasis. Although the observed trend is promising, the effect of the epistasis is weak and unstable from family to family. Thus, more deep tuning of heat shock regimes is needed to uncover the most efficient combination of factors (absolute temperature, duration, stage of the embryo development) aggravating the burden of deleterious mutations and thus exposing them to the selection.

The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra between different organisms is still incomprehensible. Since mitochondria are responsible for aerobic respiration, it is expected that mtDNA mutational spectrum is affected by oxidative damage. Assuming that oxidative damage increases with age, we analyse mtDNA mutagenesis of different species in regards to their generation length. Analysing, (i) dozens of thousands of somatic mtDNA mutations in samples of different ages (ii) 70053 polymorphic synonymous mtDNA substitutions reconstructed in 424 mammalian species with different generation lengths and (iii) synonymous nucleotide content of 650 complete mitochondrial genomes of mammalian species we observed that the frequency of AH > GH substitutions (H: heavy strand notation) is twice bigger in species with high versus low generation length making their mtDNA more AH poor and GH rich. Considering that AH > GH substitutions are also sensitive to the time spent single-stranded (TSSS) during asynchronous mtDNA replication we demonstrated that AH > GH substitution rate is a function of both species-specific generation length and position-specific TSSS. We propose that AH > GH is a mitochondria-specific signature of oxidative damage associated with both aging and TSSS.

Here, we synthesize a Au@Fe

Heterodimeric nanoparticles comprising materials with different functionalities are of great interest for fundamental research and biomedical/industrial applications. In this work, Fe3O4-Au nano-heterostructures were synthesized by a one-step thermal decomposition method. The hybrid nanoparticles comprise a highly crystalline 12 nm magnetite octahedron decorated with a single noble metal sphere of 6 nm diameter. Detailed analysis of the nanoparticles was performed by UV-visible spectroscopy, magnetometry, calorimetry and relaxometry studies. The cytotoxic effect of the nanoparticles in the human hepatic cell line Huh7 and PLC/PRF/5-Alexander was also assessed. These Fe3O4-Au bifunctional nanoparticles showed no significant cytotoxicity in these two cell lines. The nanoparticles showed a good theranostic potential for liver cancer treatment, since the r2 relaxivity (166.5 mM−1·s−1 and 99.5 mM−1·s−1 in water and HepG2 cells, respectively) is higher than the corresponding values for commercial T2 contrast agents and the Specific Absorption Rate (SAR) value obtained (227 W/gFe) is enough to make them suitable as heat mediators for Magnetic Fluid Hyperthermia. The gold counterpart can further allow the conjugation with different biomolecules and the optical sensing.