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Biology subjects

Sokolova, E.

Publications and source records attributed to Sokolova, E..

4 recordsLinked to original sources

The First Experience of Accelerator-based Lithium Neutron Capture Therapy in vivo

Boron neutron capture therapy (BNCT) is one of the promising treatment methods for cancer. BNCT is based on the unique high ability of the non-radioactive boron-10 (10B) nucleus to absorb thermal neutrons. The absorption of a neutron by boron results in a nuclear reaction 10B(n,)7Li with 84% of the energy being released within the cell, thereby inducing cancer cell death. We propose a novel approach based on using lithium instead of boron in neutron capture therapy: the neutron capture reaction cross-section for lithium is 4 times smaller than that of boron, while the energy release is 2 times higher, and the primary advantage of lithium is that 100% of the energy is released inside the cell. A series of in vivo neutron irradiation experiments using the murine B16 skin melanoma model demonstrated the efficacy of lithium neutron capture therapy (LiNCT). Higher lithium concentrations in the tumor achieved through intraperitoneal administration, compared to the oral route, contributed to a significant increase in animal survival and a significant decrease in tumor growth. The results of our study provide entirely new opportunities for the development of neutron capture therapy, both with lithium and with a possible lithium-boron combination.

biophysics↗

Development of a marker within the candidate Un8 true loose smut resistance gene for use in barley breeding

Breeding for resistance to true loose smut infection caused by the pathogen (Ustilago nuda (Jens.) Rostr.) is an economical and environmentally safe way to limit the effect of this pathogen on barley. However, screening for resistance using natural infection can lead to inconsistent results and artificial inoculation is labour intensive, and can fail, leading to erroneous phenotyping. Marker assisted selection of genes conferring disease resistance can increase the efficiency of breeding programs. A candidate gene for Un8 resistance was used to develop a genetic marker which was tested on a recombinant inbred line (RIL) population derived from the resistant CDC Freedom and the susceptible Samson varieties. The RIL population (98 lines) was phenotyped for resistance to true loose smut by artificial inoculation and genotyped with the newly developed marker. The genotyping results obtained with the marker developed in this study were mostly consistent with true loose smut resistance determined by artificial inoculation. The markers was also tested in additional barley cultivars and breeding material. Repeated analysis of inconsistent results is required to confirm or revise these results, as well as further investigation of the candidate gene to confirm its role in barley true loose smut resistance is being planned.

plant biology↗

Eukaryotic ribosome recognizes 3 context and stimulates stop codon readthrough

It is known that the nucleotide context surrounding stop codons significantly affects the efficiency of translation termination. In eukaryotes, various 3' contexts have been described that are unfavourable for translation termination; however, the exact molecular mechanism that mediates their effect remains unknown. In this study, we used a reconstituted mammalian translation system to examine the efficiency of stop codons in different contexts, including several previously described weak 3' stop codon contexts. Our results revealed that ribosomes can independently recognize certain contexts and ignore stop codons that are followed by these sequences. Moreover, the efficiency of translation termination at the weak 3' contexts was almost equal to the one at the standard context. We propose that weak 3' contexts interact with the 18S rRNA provoking a conformational change in the U-turn-like structure of the stop codon in the A site of ribosome. This change makes incorporation of the near-cognate tRNA more preferable than recognition of the stop codon by the release factors and increases readthrough.

molecular biology↗

Nsp1 of SARS-CoV-2 Stimulates Host Translation Termination

The Nsp1 protein of SARS-CoV-2 regulates the translation of host and viral mRNAs in cells. Nsp1 inhibits host translation initiation by occluding the entry channel of the 40S ribosome subunit. The structural study of SARS-CoV-2 Nsp1-ribosomal complexes reported post-termination 80S complex containing Nsp1 and the eRF1 and ABCE1 proteins. Considering the presence of Nsp1 in the post-termination 80S ribosomal complex simultaneously with eRF1, we hypothesized that Nsp1 may be involved in translation termination. Using a cell-free translation system and reconstituted in vitro translation system, we show that Nsp1 stimulates translation termination in the stop codon recognition stage at all three stop codons. This stimulation targets the release factor 1 (eRF1) and does not affect the release factor 3 (eRF3). The activity of Nsp1 in translation termination is provided by its N-terminal domain and the minimal required part of eRF1 is NM domain. We assume that biological meaning of Nsp1 activity in translation termination is binding with the 80S ribosomes translating host mRNAs and removal them from the pool of the active ribosomes.

molecular biology↗