[Pharmacogenetic aspects of the dopaminergic system in clozapine pharmacodynamics]. / Farmakogeneticheskie aspekty dofaminergicheskoi sistemy v farmakodinamike klozapina.

A systematic review of association studies on the role of single nucleotide variants (SNVs) of the dopaminergic system genes on the effectiveness of clozapine in schizophrenia has been perfromed. A search of literature was conducted in PubMed, MedLine, Web of Science Core Collection (Clarivate Analytics), Web of Science, Russian Science Citation Index, Scopus, Scientific Research, Google Scholar, Oxford Press, e-Library from 1995-2019. Association studies of 53 SNPs of genes encoding dopamine receptor isoforms (DRD1), dopamine transporter (SCL6A3) and catechol-O- methyltransferase (COMT), and the nature of their association with the therapeutic response to clozapine were analyzed. The results of SNPs studies of DRD1 and COMT genes are the most controversial. This can be explained by the heterogeneity of the samples and the lack of standardization of methods for evaluating the effectiveness of treatment in the context of association studies. The clear population specificity of the association of some SNPs of DRD1, DRD2 and DRD3 genes with the response to clozapine therapy has been shown. Most of the identified associations are haplotype specific. The obtained regularities of the effect of SNPs of dopaminergic system genes on the effectiveness of clozapine therapy should be considered in an individual approach to treatment of schizophrenia.

Duality in Power-Law Localization in Disordered One-Dimensional Systems.

The transport of excitations between pinned particles in many physical systems may be mapped to single-particle models with power-law hopping, 1/r^{a}. For randomly spaced particles, these models present an effective peculiar disorder that leads to surprising localization properties. We show that in one-dimensional systems almost all eigenstates (except for a few states close to the ground state) are power-law localized for any value of a>0. Moreover, we show that our model is an example of a new universality class of models with power-law hopping, characterized by a duality between systems with long-range hops (a<1) and short-range hops (a>1), in which the wave function amplitude falls off algebraically with the same power γ from the localization center.

Influence of nanosilver on the efficiency of Pisum sativum crops germination.

The study is aimed to investigate the impact of silver nanoparticles on germination of Pisum sativum pea seeds. The influence of synthesized silver nanoparticles on root length and percentage of germinated seeds was revealed. It was found that nanosilver treatment agents do not affect the germination of pea seeds negatively at low concentrations. Also, the treatment of pea seeds with silver nanoparticles provide a significant positive effect on the root length of pea seeds.

Phase coexistence and electric-field control of toroidal order in oxide superlattices.

Systems that exhibit phase competition, order parameter coexistence, and emergent order parameter topologies constitute a major part of modern condensed-matter physics. Here, by applying a range of characterization techniques, and simulations, we observe that in PbTiO3/SrTiO3 superlattices all of these effects can be found. By exploring superlattice period-, temperature- and field-dependent evolution of these structures, we observe several new features. First, it is possible to engineer phase coexistence mediated by a first-order phase transition between an emergent, low-temperature vortex phase with electric toroidal order and a high-temperature ferroelectric a1/a2 phase. At room temperature, the coexisting vortex and ferroelectric phases form a mesoscale, fibre-textured hierarchical superstructure. The vortex phase possesses an axial polarization, set by the net polarization of the surrounding ferroelectric domains, such that it possesses a multi-order-parameter state and belongs to a class of gyrotropic electrotoroidal compounds. Finally, application of electric fields to this mixed-phase system permits interconversion between the vortex and the ferroelectric phases concomitant with order-of-magnitude changes in piezoelectric and nonlinear optical responses. Our findings suggest new cross-coupled functionalities.

Nonergodic Phases in Strongly Disordered Random Regular Graphs.

We combine numerical diagonalization with semianalytical calculations to prove the existence of the intermediate nonergodic but delocalized phase in the Anderson model on disordered hierarchical lattices. We suggest a new generalized population dynamics that is able to detect the violation of ergodicity of the delocalized states within the Abou-Chakra, Anderson, and Thouless recursive scheme. This result is supplemented by statistics of random wave functions extracted from exact diagonalization of the Anderson model on ensemble of disordered random regular graphs (RRG) of N sites with the connectivity K=2. By extrapolation of the results of both approaches to N→∞ we obtain the fractal dimensions D_{1}(W) and D_{2}(W) as well as the population dynamics exponent D(W) with the accuracy sufficient to claim that they are nontrivial in the broad interval of disorder strength W_{E}10^{5} reveals a singularity in D_{1,2}(W) dependencies which provides clear evidence for the first order transition between the two delocalized phases on RRG at W_{E}≈10.0. We discuss the implications of these results for quantum and classical nonintegrable and many-body systems.

Role of Hematopoietic Stem Cells in Inflammation of the Pancreas during Diabetes Mellitus.

The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing ß-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL-1ß and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor ß-cells (CD45(-), TER119(-), c-kit-1(-), and Flk-1(-)), oligopotent progenitor ß-cells (CD45(-), TER119(-), CD133(+), and CD49f(low)), and insulinproducing ß-cells (Pdx1(+)). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin-Sca-1(+)c-kit(+)CD34(+)) relative to long-term cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5-fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice.

Multifractality of random eigenfunctions and generalization of Jarzynski equality.

Systems driven out of equilibrium experience large fluctuations of the dissipated work. The same is true for wavefunction amplitudes in disordered systems close to the Anderson localization transition. In both cases, the probability distribution function is given by the large-deviation ansatz. Here we exploit the analogy between the statistics of work dissipated in a driven single-electron box and that of random multifractal wavefunction amplitudes, and uncover new relations that generalize the Jarzynski equality. We checked the new relations theoretically using the rate equations for sequential tunnelling of electrons and experimentally by measuring the dissipated work in a driven single-electron box and found a remarkable correspondence. The results represent an important universal feature of the work statistics in systems out of equilibrium and help to understand the nature of the symmetry of multifractal exponents in the theory of Anderson localization.

Anderson localization on the Bethe lattice: nonergodicity of extended States.

Statistical analysis of the eigenfunctions of the Anderson tight-binding model with on-site disorder on regular random graphs strongly suggests that the extended states are multifractal at any finite disorder. The spectrum of fractal dimensions f(α) defined in Eq. (3) remains positive for α noticeably far from 1 even when the disorder is several times weaker than the one which leads to the Anderson localization; i.e., the ergodicity can be reached only in the absence of disorder. The one-particle multifractality on the Bethe lattice signals on a possible inapplicability of the equipartition law to a generic many-body quantum system as long as it remains isolated.

Magnetic field-induced giant enhancement of electron-phonon energy transfer in strongly disordered conductors.

Relaxation of soft modes (e.g., charge density in gated semiconductor heterostructures, spin density in the presence of magnetic field) slowed down by disorder may lead to giant enhancement of energy transfer (cooling power) between overheated electrons and phonons at low bath temperature. We show that in strongly disordered systems with time-reversal symmetry broken by external or intrinsic exchange magnetic field the cooling power can be greatly enhanced. The enhancement factor as large as 10(2) at magnetic field B~10 T in 2D InSb films is predicted. A similar enhancement is found for the ultrasound attenuation.

Lévy flights and multifractality in quantum critical diffusion and in classical random walks on fractals.

We employ the method of virial expansion to compute the retarded density correlation function (generalized diffusion propagator) in the critical random matrix ensemble in the limit of strong multifractality. We find that the long-range nature of the Hamiltonian is a common root of both multifractality and Lévy flights, which show up in the power-law intermediate- and long-distance behaviors, respectively, of the density correlation function. We review certain models of classical random walks on fractals and show the similarity of the density correlation function in them to that for the quantum problem described by the random critical long-range Hamiltonians.

Immunocytochemical study of Helicobacter pylori in the mucosae of the gastric antrum and rectum.

We present the results of bacterioscopic and immunocytochemical study of Helicobacter pylori in biopsy specimens from the gastric antrum and smears from the rectum. Predominance of spiral-shaped vegetative form of Helicobacter pylori in the antrum and the presence of cocci with Helicobacter pylori antigens in smears from the rectum were demonstrated in patients infected with Helicobacter pylori. The diagnostic sensitivity of non-invasive immunocytochemical Helicobacter pylori test in rectal smears was 90%, specificity 76%, and efficiency of the test 84%.

Cox-2 immunohistochemical expression in epithelial ovarian carcinoma and platin sensitivity.

PURPOSE: The aim of the study was to assess whether COX-2 expression in epithelial ovarian carcinoma (EOC) tissue can distinguish between platin-sensitive and platin-resistant tumors. METHODS: Clinical and histological data were obtained from medical records of EOC patients diagnosed between the years 1995 and 2005. Patients in complete clinical remission for > 6 months after discontinuation of first-line chemotherapy were considered to be platin-sensitive. Survival of < or = 2 and > 5 years after diagnosis was considered as short- and long-term survival, respectively. Immunohistochemistry staining was performed on deparaffinized sections of tissue blocks obtained at first surgery. The intensity of staining and the percentage of stained cells was assessed by two pathologists blinded to clinical data and a scoring index was calculated. RESULTS: Among 79 patients a positive stain (> 10% of cells stained) was observed in 61 (77.2%). No statistically significant association between distribution of platin sensitivity and immunohistochemical COX-2 staining parameters was observed, although the rate of long-term survival was significantly higher among platin-sensitive then among platin-resistant/unresponsive patients. CONCLUSIONS: Immunohistochemically determined COX-2 expression in EOC is not associated with platin sensitivity and survival.

[The reentrant binomial model of nuclear anomalies growth in rhabdomyosarcoma RA-23 cell populations under increasing doze of rare ionizing radiation].

Distributions of nuclear morphology anomalies in transplantable rabdomiosarcoma RA-23 cell populations were investigated under effect of ionizing radiation from 0 to 45 Gy. Internuclear bridges, nuclear protrusions and dumbbell-shaped nuclei were accepted for morphological anomalies. Empirical distributions of the number of anomalies per 100 nuclei were used. The adequate model of reentrant binomial distribution has been found. The sum of binomial random variables with binomial number of summands has such distribution. Averages of these random variables were named, accordingly, internal and external average reentrant components. Their maximum likelihood estimations were received. Statistical properties of these estimations were investigated by means of statistical modeling. It has been received that at equally significant correlation between the radiation dose and the average of nuclear anomalies in cell populations after two-three cellular cycles from the moment of irradiation in vivo the irradiation doze significantly correlates with internal average reentrant component, and in remote descendants of cell transplants irradiated in vitro - with external one.

[Micronuclei in mucose cells and colonization of human stomach epithelium with coccoid forms of Helicobacter pylori].

International Agency for Research on Cancer recognized as sufficient the evidence of Helicobacter pylori (HP) infection carcinogenicity and placed it into the 1 st group of carcinogens. Micronucleus level in gastric epithelial cells of antral stomach region of patients with chronic non-atrophy gastritis (n = 62) was studied. 40 patients of 62 had HP-associated gastritis. The HP-bacterium exists in a spiral and coccoid form. Both morphological forms were examined using immunocytochemistry. Significantly increased micronucleus number was observed in the cells of HP-infected patients compared with non-infected person (P < 0.05). The frequency of stomach epithelium cells with micronuclei was enhanced considerably in the patients infected with the coccoid HP form. Therefore the patients with HP-associated chronic gastritis caused by the coccoid form with high degree of colonization must be considered as a group of enhanced risk of gastric carcinogenesis.

[The study of DNA integrity in somatic cells and spermatozoa by single cell gel electrophoresis with silver staining].

In present work we studied DNA damage in human and bovine lymphocytes and spermatozoa by means of single cell gel electrophoresis followed by silver staining. The spontaneous frequency of DNA damage estimated manually in spermatozoa from healthy donors did not exceed 9% (on average -- 4.8 +/- 1.2%). The frequency of DNA damages in bull sperm after short (less than a year) and long period (more than 20 years) of cryopreservation was assessed as 3.1 +/- 0.9 and 4.3 +/- 0.5%, correspondingly. The comparative estimation of DNA damages in lymphocytes followed by silver staining is a valuable tool to estimate DNA damage in populations of somatic and reproductive cells.

[Immunomorphological characteristics and criteria for predicting gastrointestinal stromal tumors].

The study of 36 cases of gastrointestinal stromal tumors (GIST) (n = 26 of the stomach and n = 10 of the duodenum, small bowel, and rectum) indicated that among the clinical symptoms, there were prevalent abdominal pains and gastrointestinal bleeding. Local invasion and metastases were detected in 11 patients. According to the risk of aggressiveness, 1 tumor presented a very low risk; 5, a low risk; 14, a moderate risk; and 16 a high risk. All GISTs with mucosal infiltration were in high and moderate risk groups. The expression of p27 did not depend on that of other markers, the sizes of a tumor, its histological type, and affinity to this or that risk group. There was a statistically significant difference in the expression of Ki-67 in the groups of low (1.7%) and high (10.3%) risks.

[Clinical and morphological characteristics of gastrointestinal stromal tumors].

GIST are stromal tumors and the gastrointestinal tract (GIT) and some other organs of spindle-cell or epithelioid-cell structure expressing CD117 (C-kit, KIT), as well as those at different rates and in different combinations, CD34, smooth muscle and/or neurogenic differentiation antigens. It should be taken into account that CD117 are also expressed by melanomas, vascular, and some other tumors. The c-kit gene mutations leading to the expression and autoactivation of the tyrosine kinase receptor KIT underlie the oncogenesis of GIST, which results in enhanced proliferative activity and inhibited apoptosis. This is supported by successful chemotherapy for GIST with a KIT receptor inhibitor. The histogenesis of GIST is associated with GIT somatic stem, the Cajal cell precursors. Many GISTs behave like sarcomas and they are characterized by an infiltrating growth, hematogenic (mainly into the liver) and implantational (along the peritoneum) cancer spread. There are opinions that all such neoplasms are potentially malignany and small-sized GISTs are benign and have the minimum mitotic activity.

Eigenfunction fractality and pseudogap state near the superconductor-insulator transition.

We develop a theory of a pseudogap state appearing near the superconductor-insulator (SI) transition in strongly disordered metals with an attractive interaction. We show that such an interaction combined with the fractal nature of the single-particle wave functions near the mobility edge leads to an anomalously large single-particle gap in the superconducting state near SI transition that persists and even increases in the insulating state long after the superconductivity is destroyed. We give analytic expressions for the value of the pseudogap in terms of the inverse participation ratio of the corresponding localization problem.

[Expression of cycline-dependent kinase p27 in the low differentiated gastric adenocarcinoma].

The authors investigated p27 expression in 21 cases of high-grade gastric adenocarcinoma with portions of signet ring cell differentiation, by comparing that in 11 cases of chronic atrophic gastritis with Helicobacter pylori and in 5 cases of the intact gastric mucosa. The mean age of patients with gastric adenocarcinoma was 67.7 years (35-86 years); there were 9 males and 12 females. All tumors were of T3 N1-2 M0 stage. Helicobacter pylori was found in 3 of the 21 patients. The investigations indicated a great difference (by 2.4-7.6 times) and a statistically significant decrease in p27 expression in the adenocarcinoma cells as compared to the comparison groups. However, there was no significant correlation between the lower level of p27 expression and the prognosis in patients with adenocarcinoma.