Vol 473, No 1 (2017)

Using Fura-2AM microfluorimetry, we have shown for the first time that preincubation of macrophages with methyl-β-cyclodextrin, inducing cholesterol extraction from membranes and raft disruption, leads to significant inhibition of thapsigargin-induced store-dependent Ca²⁺ entry in rat peritoneal macrophages. In contrast, macrophage treatment with methyl-β-cyclodextrin after Ca²⁺ entry mechanisms were activated by store depletion by thapsigargin application leads to potentiation of subsequent store-dependent Ca²⁺ entry. The results suggest that intact lipid rafts are necessary for the activation but not the maintenance of store-dependent Ca²⁺ entry in macrophages.

The study addresses the influence of the physicochemical properties of the reserve cellular macromolecules (polyhydroxyalkanoates, PHA) with different chemical composition on their biodegradation in the agro-transformed field soil of the Siberian region (Krasnoyarsk Territory, Russia). It was shown that the degradation of the PHA samples depends on the degree of polymer crystallinity (C_x). For the first time, it was shown that the range of PHA-degrading microorganisms differs for each of PHA types. The study defines the primary degraders specific to each PHA type and common to all types of examined polymers.

Larva, prepupa (last instar larva), pupa, and an empty shell of pupa after hatching of the black soldier fly Hermetia illucens contain eumelanin, an active synthesis of which is observed at the prepupal stage, which is probably due to the release of prepupa from the feed substrate thickness to the open space for pupation. It was shown for the first time that prepupa contains high quantities of the magnetically active form of manganese Mn²⁺. This fact indicates that Mn²⁺ stimulates the copper-containing tyrosinase—the key enzyme in the synthesis of melanin in the period of migration and adaptation of the insect to the solar radiation.

Genes encoding six chitinases, five of which belong to classes I (MhCHI3 and MhCHI4), IV (MhCHI1), V (MhCHI5), and VII (MhCHI2), were identified in the transcriptome of the parasitic mixoheterotrophic plant Monotropa hypopitys. The transcription level of MhCHI5 and MhCHI1 was low; however, in the leaves (bracts) and roots it was higher than in flowers. MhCHI4 transcripts were detected primarily in the flowers and were almost absent in the roots, whereas the expression level of MhCHI3 was relatively high in all organs but maximum in the leaves (bracts).

The study of the effect of vasodilator, antiplatelet agent, and inhibitor P-glycoprotein dipyridamole (DIP) on the functioning of the transmembrane protein of the reaction center (RC) of Rb. sphaeroides showed that the activation of RC by constant light generates the DIP radical cation, which significantly affects the kinetics of recombination of charges divided between photoactive bacteriochlorophyll and quinone acceptors. Thus, the antioxidant properties of DIP may affect the functional activity of membrane proteins, and this apparently should be taken into account in the studies of the mechanisms of therapeutic action of this drug.

The hERG potassium channel is one of the most important anti-targets determining cardiotoxicity of potential drugs. Using fragmental descriptors and artificial neural networks, the predictive models of the relationship between the structure of organic compounds and their activity with respect to hERG were built, and the structural factors affecting it were analyzed. By their predictive ability and applicability domain, these models (N = 1000, Q² = 0.77, RMSE_cv = 0.45 for affinity and N = 2886, Q² = 0.60, RMSE_cv = 0.55 for channel inhibition) are superior to the previously published models and can be used to minimize the risk of cardiotoxicity during drug development.

The use of the mathematical model of rat nociceptive neuron membrane allowed us to predict a new mechanism of suppression of ectopic bursting discharges, which arise in neurons of dorsal root ganglia and are one of the causes of neuropathic pain. The treatment with comenic acid leads to switching off the ectopic bursting discharges due to a decrease in the effective charge transferring via the activation gating structure of the slow sodium channels (Na_V1.8a). Comenic acid is a drug substance of a new non-opioid analgesic [1] Thus, this analgesic not only reduces the frequency of rhythmic discharges of nociceptive neuron membrane [2] but also it suppresses its ectopic bursting discharges.

We found that an increase in the expression level of E75, DHR3, and ERR increases the degree of activation of dhr3 and hr4 genes in Drosophila S2 cells. We also detected a repressing effect of these nuclear receptors on the basal transcription level of these genes. This is the first study to show the ability of nuclear receptors E75, DHR3, and ERR to function as activators or repressors depending on external conditions. We also confirmed the existence of the interaction of all studied nuclear receptors with the promoters of dhr3 and hr4 genes of the ecdysone cascade in vivo.

It was shown that the neuroactive peptide 5-oxo-Pro-Arg-Pro (5-oxo-PRP) is detected in the brain in the time interval of 5–120 min after it was intravenously or intranasally administered to rats; the maximum concentration of labeled tripeptide in these modes of administration was observed after 30 and 10 min, respectively. A significant difference in the concentrations of 5-oxo-PRP in the blood and brain (the latter was 50 times lower) during intravenous administration indicates a relatively low permeability of the peptide across the blood–brain barrier. Pharmacokinetic data analysis showed that, when administered intranasally, approximately 45% of the total number of 5-oxo-PRP detectable in the brain in the entire period of study enters via transport from the nasal cavity, and the rest of the peptide enters through the blood–brain barrier from the blood stream. It was found that 5-oxo-PRP in rats is rapidly metabolized forming proteolytic products, mainly amino acids, and degradation products, presumably oxidized these amino acids.