Buryat Language in Multi-Ethnic Buryatia: Functional Distribution, Language Competence, Motivations

The analysis of some of the results of a sociolinguistic survey conducted in 2020 in the Republic of Buryatia is presented in the article. A feature of this survey is a large sample (1289 respondents of Buryat and Russian nationality) and a wide coverage of the problems of the functioning of the Buryat language. A comparative analysis with the results of previous surveys showed that the level of proficiency in the native language of the Buryats and the degree of its use in various areas of communication continues to decline. A positive and tolerant attitude to the study of the Buryat language on the part of the Russian population was revealed, while at the same time a low assessment of its “necessity” by both Russians and Buryats. A causal relationship has been established between the compulsory teaching of the Buryat language in schools and an increase in the number of people who read and write in Buryat. It was revealed that when choosing a language of study, territorial motivation is the main one for Russians, for Buryats it is the motivation of ethnic identity. At the same time, the ethnoidentification factor has recently lost its significance, which is manifested in a high level of dual (ethno) linguistic identification and a decrease in the number of Buryats who consider the Buryat language to be their native language

New Hydrazinothiazole Derivatives of Usnic Acid as Potent Tdp1 Inhibitors.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising therapeutic target in cancer therapy. Combination chemotherapy using Tdp1 inhibitors as a component can potentially improve therapeutic response to many chemotherapeutic regimes. A new set of usnic acid derivatives with hydrazonothiazole pharmacophore moieties were synthesized and evaluated as Tdp1 inhibitors. Most of these compounds were found to be potent inhibitors with IC50 values in the low nanomolar range. The activity of the compounds was verified by binding experiments and supported by molecular modeling. The ability of the most effective inhibitors, used at non-toxic concentrations, to sensitize tumors to the anticancer drug topotecan was also demonstrated. The order of administration of the inhibitor and topotecan on their synergistic effect was studied, suggesting that prior or simultaneous introduction of the inhibitor with topotecan is the most effective

Mammalian Base Excision Repair: Functional Partnership between PARP-1 and APE1 in AP-Site Repair

<div><p>The apurinic/apyrimidinic- (AP-) site in genomic DNA arises through spontaneous base loss and base removal by DNA glycosylases and is considered an abundant DNA lesion in mammalian cells. The base excision repair (BER) pathway repairs the AP-site lesion by excising and replacing the site with a normal nucleotide via template directed gap-filling DNA synthesis. The BER pathway is mediated by a specialized group of proteins, some of which can be found in multiprotein complexes in cultured mouse fibroblasts. Using a DNA polymerase (pol) β immunoaffinity-capture technique to isolate such a complex, we identified five tightly associated and abundant BER factors in the complex: PARP-1, XRCC1, DNA ligase III, PNKP, and Tdp1. AP endonuclease 1 (APE1), however, was not present. Nevertheless, the complex was capable of BER activity, since repair was initiated by PARP-1’s AP lyase strand incision activity. Addition of purified APE1 increased the BER activity of the pol β complex. Surprisingly, the pol β complex stimulated the strand incision activity of APE1. Our results suggested that PARP-1 was responsible for this effect, whereas other proteins in the complex had no effect on APE1 strand incision activity. Studies of purified PARP-1 and APE1 revealed that PARP-1 was able to stimulate APE1 strand incision activity. These results illustrate roles of PARP-1 in BER including a functional partnership with APE1.</p></div

A model illustrating APE1-dependent and-independent mammalian BER coordinated by BER factors in the pol β complex.

<p>AP-site lesions in DNA that are formed by spontaneous hydrolysis of the <i>N</i>-glycosylic bond or by removal of inappropriate bases by DNA <i>N</i>-glycosylases are recognized by PARP-1 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124269#pone.0124269.ref044" target="_blank">44</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124269#pone.0124269.ref050" target="_blank">50</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124269#pone.0124269.ref061" target="_blank">61</a>]. By virtue of the presence of PARP-1 in the pol β complex, the complex is recruited to the AP-site in DNA. Upon binding to AP-site, PARP-1 is auto-poly(ADP-ribosyl)ated [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124269#pone.0124269.ref044" target="_blank">44</a>]. While the complex remains bound to the AP-site DNA strand, BER may proceed either by an APE1-dependent (<i>left-hand</i> side of the scheme) or APE1-independent (<i>right-hand</i> side of the scheme) pathway. In the case of the APE1-dependent pathway, APE1 incises the AP-site, while the complex is still bound to the AP-site. The dRP removal, DNA synthesis and ligation steps are conducted. On the other hand, in situations where APE1 is deficient, APE1-independent BER operates where PNKP plays a central role [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124269#pone.0124269.ref060" target="_blank">60</a>]. In this case, for example, the complex bound at the AP-site incises the DNA strand by its PARP-1’s lyase activity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124269#pone.0124269.ref050" target="_blank">50</a>]. Tdp1 and/or PNKP trim or edit the 3′blocked group to generate the 3′-OH necessary for the DNA synthesis and ligation steps, respectively. PAPR-1 is depicted as the blue triangle in the pol β complex.</p