I Võidupüha mälestus

Digiteeritud Euroopa Regionaalarengu Fondi rahastusel, projekti "Eesti teadus- ja õppekirjandus" (2014-2020.12.03.21-0848) raames.https://www.ester.ee/record=b1157529*es

ATR–Chk1 signaling pathway and homologous recombinational repair protect cells from 5-fluorouracil cytotoxicity

5-Fluorouracil (5-FU) has long been a mainstay antimetabolite chemotherapeutic drug for the treatment of major solid tumors, particularly colorectal cancer. 5-FU is processed intracellularly to yield active metabolites that compromise RNA and DNA metabolism. However, the mechanisms responsible for its cytotoxicity are not fully understood. From the phenotypic analysis of mutant chicken B lymphoma DT40 cells, we found that homologous recombinational repair (HRR), involving Rad54 and BRCA2, and the ATR–Chk1 signaling pathway, involving Rad9 and Rad17, significantly contribute to 5-FU tolerance. 5-FU induced γH2AX nuclear foci, which were colocalized with the key HRR factor Rad51, but not with DNA double-strand breaks (DSBs), in a dose-dependent manner as cells accumulated in the S phase. Inhibition of Chk1 kinase by UCN-01 increased 5-FU-induced γH2AX and enhanced 5-FU cytotoxicity not only in wild-type cells but also in Rad54- or BRCA2-deficient cells, suggesting that HRR and Chk1 kinase have non-overlapping roles in 5-FU tolerance. 5-FU-induced Chk1 phosphorylation was significantly impaired in Rad9- or Rad17-deficient cells, and severe γH2AX nuclear foci and DSBs were formed, which was followed by apoptosis. Finally, inhibition of Chk1 kinase by UCN-01 increased 5-FU-induced γH2AX nuclear foci and enhanced 5-FU cytotoxicity in Rad9- or Rad17-deficient cells. These results suggest that Rad9- and Rad17-independent activation of the ATR–Chk1 signaling pathway also significantly contributes to 5-FU tolerance

Age‐dependent expression of cancer‐related genes in a long‐lived seabird

International audienceStudies of model animals like mice and rats have led to great advances in our understanding of the process of tumorigenesis, but this line of study has less to offer for understanding the mechanisms of cancer resistance. Increasing the diversity of nonmodel species from the perspective of molecular mechanisms of natural cancer resistance can lead to new insights into the evolution of protective mechanisms against neoplastic processes and to a wider understanding of natural cancer defense mechanisms. Such knowledge could then eventually be harnessed for the development of human cancer therapies. We suggest here that seabirds are promising, albeit currently completely ignored candidates for studying cancer defense mechanisms, as they have a longer maximum life span than expected from their body size and rates of energy metabolism and may have thus evolved mechanisms to limit neoplasia progression, especially at older ages. We here apply a novel, intraspecific approachof comparing old and young seabirds for improving our understanding of aging and neoplastic processes in natural settings. We used the long-lived common gulls (Larus canus) for studying the age-related pattern of expression of cancer-related genes, based on transcriptome analysis and databases of orthologues of human cancer genes. The analysis of differently expressed cancer-related genes between young and old gulls indicated that similarly to humans, age is potentially affecting cancer risk in this species. Out of eleven differentially expressed cancer-related genes between the groups, three were likely artifactually linked to cancer. The remaining eight were downregulated in old gulls compared to young ones. The downregulation of five of them could be interpreted as a mechanism suppressing neoplasia risk and three as increasing the risk. Based on these results, we suggest that old gulls differ from young ones both from the aspect of cancer susceptibility and tumor suppression atthe genetic level

Study of the structural curvature in Mo2C derived carbons with contrast matched small angle neutron scattering

The influence of the synthesis conditions on the formation of the porous and the graphitic structure of carbon materials was investigated on Mo2C derived carbon materials synthesized at different temperatures Tsyn from 700 to 1000 C . Contrast matched small angle neutron scattering method was used to obtain explicit information about the pore and pore wall structure of the carbons. It was found that carbons formed at lower Tsyn exhibit prevalently nano scale cylindrical geometry and an increase in Tsyn promotes the formation of slit like structures. Additionally, partial contrast matching was used, which effectively made the pore walls wider, enabled to hide the smaller pores, exposing in greater detail the geometries of larger mesopores. The geometry of larger structures e.g. pores and pore walls changes from mixed cylindrical and slit like to completely slit like with the increase of Tsyn. The observed change of the geometries, expressed by the increase in the dimensionality parameter, that increases from 1.2 to 1.8, empirically correlates with the decrease in the disorder between graphitic layers. Thus, we conclude that the cylindrical structures are caused by the curvature in graphitic layers formed at lower Tsyn lt;800