Morphogenetic Effects of Resettlement of Mole Voles (<Emphasis Type="Italic">Ellobius talpinus</Emphasis> Pall., 1770) from the Southern Population to the Northern Boundary of the Species Range

Geometric morphometry has been used to reveal transformations of mandible morphogenesis in the offspring of mole voles resettled to the northern part of the species range from a southern population. The transformations were new compared to both the original (southern) and the aboriginal (northern) populations. A significant increase in the intragroup morphological disparity estimated by the mean nearest neighbor distance (MNND) in the resettled animals compared to both aboriginal populations is an indirect indication of an increased developmental instability in the resettled animals exposed to new climatic conditions.     

Macroscopic fluctuations in the alcohol dehydrogenase reaction

When studying alcohol dehydrogenase reaction spontaneous oscillations of reaction rate were revealed. The value of these fluctuations essentially exceeded measuring error. The fluctuation amplitude had the maximum value when minimum buffer concentrations were used. Distribution of fluctuations according to their values was polymodal in all experiments. These oscillations seem to be classified as "macroscopic fluctuations" which have been revealed by S. Shnoll & coll [3].     

DNA with damage in both strands as affinity probes and nucleotide excision repair substrates

Nucleotide excision repair (NER) is a multistep process of recognition and elimination of a wide spectrum of damages that cause significant distortions in DNA structure, such as UV-induced damage and bulky chemical adducts. A series of model DNAs containing new bulky fluoro-azidobenzoyl photoactive lesion dC^FAB and well-recognized nonnucleoside lesions nFlu and nAnt have been designed and their interaction with repair proteins investigated. We demonstrate that modified DNA duplexes dC^FAB/dG (probe I), dC^FAB/nFlu₊₄ (probe II), and dC^FAB/nFlu_?3 (probe III) have increased (as compared to unmodified DNA, umDNA) structure-dependent affinity for XPC—HR23B (Kd_um > Kd_I > Kd_II ≈ Kd_III) and differentially crosslink to XPC and proteins of NER-competent extracts. The presence of dC^FAB results in (i) decreased melting temperature (ΔT_m = ?3°C) and (ii) 12° DNA bending. The extended dC^FAB/dG-DNA (137 bp) was demonstrated to be an effective NER substrate. Lack of correlation between the affinity to XPC—HR23B and substrate properties of the model DNA suggests a high impact of the verification stage on the overall NER process. In addition, DNAs containing closely positioned, well-recognized lesions in the complementary strands represent hardly repairable (dC^FAB/nFlu₊₄, dC^FAB/nFlu_?3) or irreparable (nFlu/nFlu₊₄, nFlu/nFlu_?3, nAnt/nFlu₊₄, nAnt/nFlu_?3) structures. Our data provide evidence that the NER system of higher eukaryotes recognizes and eliminates damaged DNA fragments on a multi-criterion basis.     

Early Anoxic Damage to the Hippocampus and Its Modifications Resulting From Chronic Influences of Antidepressants

We examined the actions of 5- or 7.5-min-long episodes of oxygen/glucose deprivation, OGD (temperature, 37°C), on pyramidal neurons of the CA1 hippocampal area and granular neurons of the gyrus dentatus. The respective damage to these neurons was manifested as an irreversible decrease in the amplitude of field EPSPs developing in such neuronal populations. Antagonists of NMDA receptors, D-2-amino-5 phosphonovaleric acid (50 μM), ketamine (50 μM), and compound TSB 24.15 (10 μM), demonstrated neuroprotective activities under these conditions, but only in the case of the 5-min-long exposure to OGD. A blocker of AMPAreceptors, DNQX (10 μM), combined with a local anesthetic, lidocaine hydrochloride (50 μM), induced comparable effects at the 7.5-min-long exposure. A blocker of calcium channels, verapamil (20 μM), exerted no effect on the level of injury of the neurons induced by the OGD influence. An inhibitor of tyrosine phosphoprotein phosphatases, sodium orthovanadate (15 mg/ml), demonstrated protective activities at both exposures, 5 and 7.5 min long. Chronic (during two weeks) preliminary injections of imipramine, fluoxetine, and pyridazol (everyday doses 20 mg/kg) into experimental animals resulted in noticeable weakening of the OGD-induced impairments of hippocapmal slices in the case of both exposures used, 5 and 7.5 min. The neuroprotective effects of chronically introduced antidepressants were augmented under the action of sodium orthovanadate. It is supposed that neuroprotective actions of preliminarily chronically introduced antidepressants with respect to the anoxic damage to hippocampal neurons is determined (at least to a considerable extent) by intensification of expression of neurotrophins. Under the influence of the latter, the functional activity of NMDA receptors decreases, and consequences of OGD-induced increase in the intracellular Ca²⁺ concentration are weakened.     

Design of oligonucleotide inhibitors for human DNA methyltransferase 1

Mammalian DNA methyltransferase 1 (Dnmt1) is responsible for copying the DNA methylation pattern during cell division. Since Dnmt1 plays an important role in carcinogenesis, it is of particular interest to search for its specific inhibitors. To design oligonucleotide inhibitors of human Dnmt1, a number of singlestranded, double-stranded, and hairpin DNA structures containing a canonical or a modified Dnmt1 recognition site (5′-CG) were constructed on the basis of a 22-nt sequence. Structural features such as a C:A mismatch, phosphorothioates, and hairpins proved capable of incrementally increasing the oligonucleotide affinity for Dnmt1. An improvement of inhibitory properties was also achieved by replacing the target cytosine with 5,6-dihydro-5-azacytosine, 5-methyl-2-pyrimidinone, or 6-methyl-pyrrolo-[2,3-d]-2-pyrimidinone. The concentration that caused 50% inhibition of methylation of 1 μM poly(dI-dC) · poly(dI-dC), a conventional DNA substrate, was approximately 10^?7 M for the most efficient oligonucleotides. Under the same in vitro conditions, these oligonucleotide inhibitors demonstrated a substantially stronger effect compared to known Dnmt1 inhibitors, which were used as controls.     

1,2,3,4-Tetrahydroisoquinolinyl sulfamic acids as phosphatase PTP1B inhibitors

High-throughput screening of the P&GP corporate repository against several protein tyrosine phosphatases identified the sulfamic acid moiety as potential phosphotyrosine mimetic. Incorporation of the sulfamic acid onto a 1,2,3,4-tetrahydroisoquinoline scaffold provided a promising starting point for PTP1B inhibitor design.     

Seasonal characteristics of gametogenesis in the Corbicula japonica

A morphological study of gonads in Corbicula japonica made it possible to distinguish between five stages of gonad maturity. It has been established that stages of active gametogenesis, prespawning and of spawning go almost in parallel and in the shortest time. In July, with the beginning of spawning, gametogenesis does not stop, and oogenesis proceeds up to the end of August. Dynamics of changes of some chemical substances in oocytes was followed. High concentrations of, respectively, RNA, albumens, lipids, glycoproteins and proteoglycans were revealed in oocyte nuclei and nucleoli both at the beginning of the development, and at the stage of active gametogenesis. This testifies in favor of a synthetic activity of these cells.     

Changes in Electrocardiographic Parameters in Males of the European North as Markers of Climate- and Age-Related Effects

Electrocardiographic (ECG) amplitude- and time-related characteristics were determined in 20- to 59-year-old healthy male residents of the European north (the zone from 60° to 70° N). They were found to display increased amplitudes of some ECG waves, as well as prolonged P waves and R–R intervals, as compared to residents of warmer regions. In men, with age, the electrical axis of the heart shifts leftward and the heart tends to rotate counterclockwise about its longitudinal axis. Increased amplitudes of the P and S waves, as well as decreased amplitudes of theQ, R, and T waves, a lower position of the ST segment relative to the isoelectric line, and a prolongation of the P wave; the P–Q, Q–T, and R–R intervals; and the ST segment were observed in most of the leads. A regional variant of the age-specific amplitude- and time-related characteristics of the ECG is suggested for healthy male residents of the north.     

Protective activity of 28-kDa 1-Cys peroxiredoxin determines its peroxidase activity]

The 28 kDa peroxiredoxin from rat exhibited peroxidase activity only in the presence of dithiothreitol. Both organic and nonorganic peroxidases were found to be substrates for the 28-kDa peroxiredoxin activity. Analysis of the protective antioxidant activity of the 28-kDa peroxiredoxin revealed that it is accounted for by its peroxidase activity.