G-Quadruplexes in Nuclear Biomolecular Condensates.

G-quadruplexes (G4s) have long been implicated in the regulation of chromatin packaging and gene expression. These processes require or are accelerated by the separation of related proteins into liquid condensates on DNA/RNA matrices. While cytoplasmic G4s are acknowledged scaffolds of potentially pathogenic condensates, the possible contribution of G4s to phase transitions in the nucleus has only recently come to light.

Modeling G4s in chromatin context confirms partial nucleosome exclusion and reveals nucleosome-disrupting effects of the least selective G4 ligands.

G-quadruplexes (G4s) are gaining increasing attention as possible regulators of chromatin packaging, and robust approaches to their studies in pseudo-native context are much needed. Here, we designed a simple in vitro model of G4-prone genomic DNA and employed it to elucidate the impact of G4s and G4-stabilizing ligands on nucleosome occupancy. We obtained two 226-bp dsDNA constructs composed of the strong nucleosome positioning sequence and an internucleosomal DNA-imitating tail.

[Pharmacological tolerance to medical therapy of organophosphate poisoning and ways of tolerance management].

Authors consider causes of low efficiency of antidote therapy and ways of pharmacological tolerance management during medical treatment of organophosphate poisoning. One of the promising ways is a preventive antidote on the base of enzyme agents and allosteric modulators of a cholinesterase activity. Authors showed a expediency of a study of new acetylcholinesterase reactivators, its compositions and ways of drug delivery.

[Study of tolerance of central muscarinic receptor blockers].

The tolerance of five central muscarinic receptor antagonists has been studied in experimental animals. According to the effect on orientation-exploratory reaction, drugs were arranged in the following order of increasing toxicity: procyclidine < trihexiphenidyl < benactizine < atropine < scopolamine. For the same therapeutic index, trihexiphenidyl and benactizine were characterized by the maximum tolerance (TD50/ED50 > 10) in mice.

[Specific features of the anticonvulsant effect of memantine in mice intoxicated with a model organic phosphate].

The effect of memantine administration has been studied on the model of mice poisoning with an anticholinesterase compound. It is established that the memantine action is due to its influence on the cholinesterase activity in the brain, blood plasma, and erythrocytes in addition to its NMDA-blocking action. Memantine promotes oxime-induced erythrocyte enzyme reactivation on the model of mice poisoning with anticholinesterase compound (0.