Super-Enhancers in the Regulation of Gene Transcription: General Aspects and Antitumor Targets.

Super-enhancers (genome elements that activate gene transcription) are DNA regions with an elevated concentration of transcriptional complexes. These multiprotein structures contain, among other components, the cyclin-dependent kinases 8 and 19. These and other transcriptional protein kinases are regarded as novel targets for pharmacological inhibition by antitumor drug candidates.

[Mechanisms of ketogenic diet action]. / Mekhanizmy deistviia ketogennoi diety.

The paper considers the necessity of using ketogenic diet and its efficacy in epilepsy. Direct and indirect effects of ketones on brain cells and molecular mechanisms of their action are discussed in detail.

Commissioning of the PRIOR proton microscope.

Recently, a new high energy proton microscopy facility PRIOR (Proton Microscope for FAIR Facility for Anti-proton and Ion Research) has been designed, constructed, and successfully commissioned at GSI Helmholtzzentrum für Schwerionenforschung (Darmstadt, Germany). As a result of the experiments with 3.5-4.5 GeV proton beams delivered by the heavy ion synchrotron SIS-18 of GSI, 30 µm spatial and 10 ns temporal resolutions of the proton microscope have been demonstrated. A new pulsed power setup for studying properties of matter under extremes has been developed for the dynamic commissioning of the PRIOR facility. This paper describes the PRIOR setup as well as the results of the first static and dynamic proton radiography experiments performed at GSI.

Analysis of informativeness of immunohistochemical and flow cytometric methods for estrogen receptor α assessment.

Informative capacity analysis of immunohistochemistry (IHC) and flow cytometry (FCM) in the assessment of estrogen receptor α (ERα) expression in breast cancer tissue was performed. Similar frequencies of expression were shown by both methods: 27% of ERα-negative and 73% ERα-positive cases. However, IHC evaluation detected low levels in only 20% of ERα-positive cases, whereas low levels of ERα detected by FCM were 2 times more often (48%). Moreover, FCM revealed positive expression (23-60%) in 33% of IHC ERα-negative cases. Among IHC ER-positive cases, zero ERα expression was detected by FCM in 12.5%. The approaches to minimize errors in routine clinical determination of the estrogen receptor status were proposed.

[Genetic control of chromosome synapsis in mice heterozygous for a paracentric inversion].

Frequencies of formation of inversion loops and their relative sizes were studied in laboratory mice heterozygous at paracentric inversion In1(1)Rk in chromosome 1, depending on the genetic background. Homozygotes In1/In1 were crossed with mice from five inbred strains (A/HeJ, BALB/cJ, C3H/HeJ, C57BL/6J, DBA2/J). The frequency of formation of inversion loops, their relative sizes, and the dependence of these parameters on the stage of pachitene were analyzed on electron-microscopic slides of spread spermatocytes in first-generation hybrids. It was shown that the genetic background and cross direction statistically significantly influenced the duration of individual pachitene stages and the frequency of inversion loops, but not relative loop size. Using a database on SNP distribution in the inbred strains examined, we carried out in silico mapping of genes affecting the genotype-dependent characters. We have found that the efficiency of synapsis in the inversion does not depend on interstrain differences in homology of the chromosome 1 region involved in the inversion. Genes controlling the inversion loop frequency in the inversion heterozygotes were mapped to chromosome 7, and genes controlling the duration of individual pachitene stages, to chromosomes 2 and 5.

[Clinical studies of vaccine TEOVac under the conditions of remote revaccination].

In the clinical trials of vaccine TEOVac in lower and reglamented doses under the conditions of remote vaccination, carried out on 11 volunteers, local reactions in the form of hyperemia, gingival edema (1 vaccinee), faucial hyperemia, enlargement of submaxillary lymph nodes (2 vaccinees) were registered in some of the vaccines; in one vaccinee systemic postvaccinal reaction of medium gravity was observed. Revaccination produced no negative effect on the hematological and biochemical characteristics of the blood, as well as on the urine characteristics. The study of the sensitizing vaccine to the antigens of the accumulation substrate (chick embryo), as well as its influence on the development of autoimmune reactions, revealed the absence of the allergic action of the preparation and its influence on autoimmune processes in the vaccines. The trial of the smallpox vaccine in tablets under the conditions of the primary immunization of adults was the topical and most promising trend in the improvement of smallpox vaccination, as the preparation TEOVac proved to be safe, in contrast to the traditional smallpox vaccine introduced by the scarification method, for both vaccines and nonimmunized persons having contacts with them.

EPR study of some rare-earth ions (Dy3+, Tb3+, and Nd3+) in YBa2Cu3O6-compound.

We investigate the low temperature X-band electron paramagnetic resonance (EPR) of YBa(2)Cu(3)O(x) compounds with x congruent with 6.0 doped with Dy(3+), Tb(3+), and Nd(3). The EPR spectra of Dy(3+) and Tb(3+) have been identified. The EPR of Tb(3+) is used also to study the effect of suppression of high T(c) superconductivity by doping with Tb(3+). The EPR of Nd(3+) is probably masked by the intense resonance of Cu(2+). All experimental EPR results compare well with theoretical estimations.

[Chromosomal evolution of the Common Shrew Sorex araneus L.from the Southern Ural and Siberia in the postglacial period]. / Khromosomnaia évoliutsiia obyknovennoi burozubki Sorex araneus L. v poslelednikovoe vremia na Iuzhnom Urale i v Sibire.

This paper summarizes a series of studies on chromosomal geography of the common shrew Sorex araneus L. in Siberia and the Southern Urals. Chromosomal races inhabiting the Southern Urals and the Western Siberian Plain sequentially replace each other in the latitudinal direction. In this region, karyotypes of each two adjacent races differ from each other by a single whole-arm reciprocal translocation. In the Eastern Siberian branch, the neighboring races differ mainly in the number or set of metacentric chromosomes. Analysis of the race distribution in the common shrew in the context of paleophysiology of the glacial period allowed us to reconstruct the sequence of events leading to the establishment of the present-day structure of the species.

Novosibirsk revisited 24 years on: chromosome polymorphism in the Novosibirsk population of the common shrew Sorex araneus L.

A Robertsonian fusion polymorphism in the common shrew (Sorex araneus L.), first described in Academgorodok near Novosibirsk (western Siberia) in 1970-72, was re-examined in 1994-95. The polymorphism in the 1970s involved chromosome arm combinations go, jl, mp and qr, i.e. each of these combinations was present in both a metacentric and a twin-acrocentric state in the population at that time. The twin-acrocentric morph for go occurred at low frequency in 1970-72 and was not observed in 1994-95. The polymorphism for arm combinations jl, mp and qr was still observed in 1994-95 and there was no significant difference in metacentric/twin-acrocentric frequencies compared with the previous sample. This is the third well-documented example in which the chromosome polymorphism in the common shrew has been found to be unchanged over a period of 20+ years. Although the polymorphism for qr may be associated with a chromosomal hybrid zone with a cline centre 200 km away, there is no definitive explanation for the other polymorphisms.

Pattern of X-Y chromosome pairing in microtine rodents.

Pairing of X and Y chromosomes at meiotic prophase in 14 species of the subfamily Microtinae (Clethrionomys rufocanus, C. rutilus, C. glareolus, Arvicola terrestris, Microtus guentheri, M. socialis, M. afghanus, M. bucharicus, M. oeconomus, M. arvalis, M. rossiaemeridionalis, M. kirgisorum, M. transcaspicus, M. (Pitymys) majori) was analysed in relation to their taxonomic position and variation in the morphology of their sex chromosomes. The sex chromosomes formed a synaptonemal complex (SC) at pachytene in all Clethrionomys species, Arvicola terrestris, and M. oeconomus, while they did not pair at all in M. (Pitymys) majori, Microtus socialis, M. guentheri, M. afghanus, M. bucharicus, M. arvalis, M. rossiaemeridionalis, M. kirgisorum, and M. transcaspicus. The X chromosome of these species varied in centromere position independently of pairing pattern. Insertion of heterochromatin of different size and location was found in some, but not in all species with asynaptic sex chromosomes. It is suggested that the sex chromosomes lost their ability to pair at male meiosis in the common ancestor of palearctic species of the genus Microtus. This event was not caused by a gross chromosomal rearrangement.

[An unusual heteromorphic bivalent in the common vole (Microtus arvalis) from Byelarus]. / Neobychnyi geteromorfnyi bivalent u obyknovennykh polevok (Microtus arvalis) iz Belorussii.

Electron microscopic analysis was carried out on the synaptonemal complexes of ten male common voles (Microtus arvalis) caught of 1990 in Byelorussia. In the early pachytene stage of spermatocytes of four males heteromorphic bivalent has been found in one of five large autosomes. In the central region of the bivalent one of the lateral elements is in the form of a D-loop, characteristic of insertion/deletion heterozygotes. However, high-resolution G-band staining of mitotic chromosomes from fibroblasts showed no significant differences in the G-band patterns between homologues.

Unusual heteromorphic bivalents in the common vole (Microtus arvalis) from Belorussia.

Electron microscopic analysis was carried out on the synaptonemal complexes of 10 male common voles (Microtus arvalis) caught in 1990 in Belorussia. In the early pachytene stage of spermatocytes of four males, a heteromorphic bivalent has been found in one of five large autosomes. In the central region of the bivalent one of the lateral elements is in the form of a D-loop, characteristic of insertion/deletion heterozygotes. However, high-resolution G-band staining of mitotic chromosomes from fibroblasts shows no significant differences in the G-band pattern between homologs.

[Adenylate kinase of plants. Properties of adenylate kinase of pea leaves]. / Adenilatkinaza rastenii. Svoistova adenilatkinazy iz list'ev gorokha

The properties of adenylate kinase in 2 ADP in equilibrium ATP + AMP reaction have been studied. The dependence of the enzyme activity on medium pH, protein concentration, substrates, Mg++ ions, AMP, adenine and adenosine has been also investigated. pH optimum is found to be 8.5 for forward reaction and 8-9--for the reverse one. The Michaelis constants are as follows: for ADP--1.17-10(-4) M, for ATP--3.33-10(-4) M at 24 degrees C, in 50 mM tris-HCl pH 7.6. The optimal ratio, Mg++ ions/substrates (ADP, ATP + AMP), is 1:2. The chelates of adenine nucleotides with Mg++ ions are proved to be "true" reaction substrates. Unlike adenine and adenosine, the product of AMP reaction inhibits adenylate kinase activity. It is concluded that the properties of adenylate kinase in plants are similar to those of animals and humans (moikinase).