Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based inhibition

Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors.     

Growth and fecundity of Daphnia after diapause and their impact on the development of a population

Laboratory and field investigations revealed that the life history traits of exephippial and parthenogenetic generations of Daphnia differ substantially. Daphniids hatching from resting eggs grow faster and their definitive body sizes are bigger than of hatchlings from subitaneous eggs. Size at maturity for exephippial animals is significantly larger. In spite of this, they mature a few days earlier than parthenogenetic females. In this study, the difference was 3–4 days for the laboratory experiments and 1–3 days for the field. Fecundity of the exephippial generation is markedly higher. Here, the clutch size for this generation was up to 3.5–4.0 times as large as for the parthenogenetic generation. Moreover, obtained results suggest that the relationship between clutch size and body length for both generations differ significantly.Estimates of the intrinsic rate of increase for field Daphnia populations demonstrated that life history traits of exephippial animals lead to a two or threefold higher rate of increase in the conditions of invertebrate predation pressure. Under moderate fish pressure, obtained r values for the daphniids hatching from resting eggs were larger than those from subitaneous. High growth rate of exephippial females is disadvantageous only under the conditions of severe pressure by fish. Obtained results suggest that hatchlings from diapausing eggs an acceleration of population increase by several times during the beginning of the development of a population with periodical re-establishment from resting eggs.     

The roles of carbonic anhydrases IX and XII in cancer cell adhesion,migration, invasion and metastasis

The main function of carbonic anhydrases (CAs) in cancer cells is the pH regulation through a conversion of H₂O and CO₂ to H⁺ and HCO₃⁻. However, the data of in vitro and in vivo studies have demonstrated that transmembrane isoforms of CA IX and CA XII are involved in various steps of cancer cell migration, invasion and metastasis. According to literature, inhibition of these CAs can affect the expression of multiple proteins. Some scientific groups have reported the possible interactions between CA IX and E-cadherin–catenin system, CA IX and integrins, CA IX, CA XII and ion transporters, which all are highly involved in cell-to-cell adhesion, the formation of membrane protrusions and focal adhesions. Nevertheless, CA IX and CA XII have a high impact on tumour growth and metastases formation. The data discussed in this review are quite recent. It highly support the role of CA IX and CA XII in various cancer metastasis processes through their interactions to other invasion proteins. Nevertheless, all findings show the great potential of these CAs in the context of research and application in clinical use.     

Interrelationships between distinct circadian manifestations of possible bruxism,perceived stress,chronotype and social jetlag in a population of undergraduate students

ABSTRACT

This study investigates the recently hypothesized association between distinct circadian manifestations of possible bruxism in subjects with different chronotype profiles, social jetlag and levels of perceived stress. A cross-sectional study was performed by surveying dental students’ of Lithuanian University of Health Sciences. A survey instrument was designed and pilot tested for reliability and validity prior to full-scale administration. The instrument consisted of four sections: socio-demographic questions, bruxism-related items, the Perceived Stress Scale and the Munich ChronoType Questionnaire. The study included 228 students (82.5% females; mean age 22.67 ± 2.27). Awake grinding was significantly associated with later chronotype values (p = 0,039). Despite the lack of significance, binary regression models demonstrated that students with later chronotypes report higher rates of possible bruxism, especially as far as awake grinding (p = .170; OR = 1.89) and sleep grinding (p = .140; OR = 1.60) are concerned. There were no significant associations between perceived stress, social jetlag and bruxism. The scores of perceived stress did not correlate with chronotype values, although a high positive correlation was found between chronotype and social jetlag (r = 0.516, p = .000). It can be concluded that later chronotypes increase the odds for self-reported bruxism, and are significantly associated with higher rates of awake grinding and social jetlag. No interrelationships were found between perceived stress, possible bruxism and social jetlag.     

Realization of the project for Acipenser oxyrhynchus oxyrhynchus restoration in the basin of the Neman River

The results of the works on the international project for the Baltic sturgeon restoration in the basin of the Neman River are considered. The mutual goal of the project is the restoration of the Baltic sturgeon population in its whole former area in the Baltic Sea. Successful works on the restoration of the Baltic sturgeon population are conducted in the Oder and the Vistula basins. The stockings of the Neman River with the sturgeon fry were started from 2012 year. It is contemplated that the sturgeon stockings of the main rivers of the Baltic Sea will enable to restore local sturgeon populations in these river basins. Till the beginning of the XXI century it was supposed that the Atlantic sturgeon Acipenser sturio had inhabited the Baltic Sea, but numerous genetic analysis of the samples of the sturgeon bones from the archeological finds in the museums showed that the Baltic Sea had been inhabited with Acipenser oxyrhynchus and its population still inhabits several rivers in Canada. This discovery permitted to start the creation of the Baltic sturgeon broodstock. Sturgeon fry from the eggs imported from Canada were used for stocking at the first stage of the project. Later it is contemplated to use the fry from the broodstocks in Germany and Poland. Sturgeon fry hatched from Canadian eggs in Poland and reared in Lithuania was used for the Neman River stocking. The fry were tagged and released in the Neris and the Sventoji Rivers in the Neman River basin. The sturgeon migrated into the Curonian lagoon where the monitoring of the catches was fulfilled. The results of sturgeon catches monitoring are discussed.     

DNA marker based identification of spontaneous hybrids between Pinus mugo and P. sylvestris at the Lithuanian sea‐side

The objective was to identify spontaneous hybrids between P. mugo and P. sylvestris using organelle DNA markers in sympatric zones at the sea‐side spit of Kursiu Nerija in western Lithuania. A field inventory was carried out over the entire Lithuanian part of the spit and 203 individuals morphologically intermediate between P. sylvestris and P. mugo were tested for their male parent with chloroplast DNA PCR‐RFLP markers and for their female parent with mitochondrial DNA PCR markers. Unfortunately, the mitochondrial DNA Nad7 marker failed to identify the female parent species in our study. However, the chloroplast DNA PCR‐RFLP marker revealed that out of 203 tested individuals only 23 had a paternity different than that indicated by morphology. Of these, 13 individuals were morphologically identified as P. sylvestris but possessed cpDNA of P. mugo (putative hybrids with P. sylvestris (female) ×P. mugo (male parent), and 10 individuals morphologically identified as P. mugo possessed cpDNA of P. sylvestris and may be hybrids with P. mugo (female) ×P. sylvestris (male parent). The remainder of the 177 individuals identified in the field inventory were were considered as pure species. In conclusion, our study indicates ongoing spontaneous hybridization between P. mugo and P. syvestris in Kursiu Nerija. Human impact via seed transfer on altered hybridization rates as well as evolutionary consequences are discussed.