Mechanisms of human DNA methylation, alteration of methylation patterns in physiological processes and oncology.

DNA methylation is one of the epigenetic modifications of the genome, the essence of which is the attachment of a methyl group to nitrogenous bases. In the eukaryote genome, cytosine is methylated in the vast majority of cases. About 98% of cytosines are methylated as part of CpG dinucleotides. They, in turn, form CpG islands, which are clusters of these dinucleotides. Islands located in the regulatory elements of genes are in particular interest. They are assumed to play an important role in the regulation of gene expression in humans. Besides that, cytosine methylation serves the functions of genomic imprinting, transposon suppression, epigenetic memory maintenance, X- chromosome inactivation, and embryonic development. Of particular interest are the enzymatic processes of methylation and demethylation. The methylation process always depends on the work of enzymatic complexes and is very precisely regulated. The methylation process largely depends on the functioning of three groups of enzymes: writers, readers and erasers. Writers include proteins of the DNMT family, readers are proteins containing the MBD, BTB/POZ or SET- and RING-associated domains and erasers are proteins of the TET family. Whereas demethylation can be performed not only by enzymatic complexes, but also passively during DNA replication. Hence, the maintenance of DNA methylation is important. Changes in methylation patterns are observed during embryonic development, aging, and cancers. In both aging and cancer, massive hypomethylation of the genome with local hypermethylation is observed. In this review, we will review the current understanding of the mechanisms of DNA methylation and demethylation in humans, the structure and distribution of CpG islands, the role of methylation in the regulation of gene expression, embryogenesis, aging, and cancer development.

White matter hyperintensity in different migraine subtypes.

The diagnostic value of white matter hyperintensities (WMH) in different types of migraineare unknown. To evaluate the WMH pattern of different subtypes in migraine patients with no vascular risk factors. 92 migraine patients (73 females, mean age 34.6 ± 8.9; 61 episodic migraine, 31 chronic migraine, 36 migraine with aura, 56 migraine without aura) without vascular risk factors underwent brain MRI (3 T). We also included a matched healthy control group with no migraine (n = 24). The prevalence of WMH in different types of migraine was similar and ranged from 38.7 to 44.4%; the control group showed no WMH at all. Lesions were located within frontal, parietal and temporal lobes (in order of decreasing incidence) in juxtacortical and/or deep white matter. WMH appeared as round or slightly elongated foci with a median size of 2.5 mm [1.5; 3]. Total number, size and prevalence of WMH by lobes and white matter regions were similar between groups, and no interaction with age or sex was found. The number of lesions within the frontal lobe juxtacortical white matter correlated with the age of patients (r = 0.331, p = 0.001) and the duration since migraine onset (r = 0.264, p = 0.012). Patients with different migraine subtypes and without vascular risk factors are characterized by a similar pattern of WMH in the absence of subclinical infarctions or microbleedings. Therefore, WMH have no relevant prognostic value regarding the course of migraine and vascular complications. WMH pattern may be used to differentiate migraine as a primary disorder and other disorders with migraine-like headache and WMH.

Amyloid properties of the yeast cell wall protein Toh1 and its interaction with prion proteins Rnq1 and Sup35.

Amyloids are non-branching fibrils that are composed of stacked monomers stabilized by intermolecular ß-sheets. Some amyloids are associated with incurable diseases, whereas others, functional amyloids, regulate different vital processes. The prevalence and significance of functional amyloids in wildlife are still poorly understood. In recent years, by applying new approach of large-scale proteome screening, a number of novel candidate amyloids were identified in the yeast Saccharomyces cerevisiae, many of which are localized in the yeast cell wall. In this work, we showed that one of these proteins, Toh1, possess amyloid properties. The Toh1-YFP hybrid protein forms detergent-resistant aggregates in the yeast cells while being expressed under its own PTOH1 or inducible PCUP1 promoter. Using bacterial system for generation of extracellular amyloid aggregates C-DAG, we demonstrated that the N-terminal Toh1 fragment, containing amyloidogenic regions predicted in silico, binds Congo Red dye, manifests 'apple-green' birefringence when examined between crossed polarizers, and forms amyloid-like fibrillar aggregates visualized by TEM. We have established that the Toh1(20-365)-YFP hybrid protein fluorescent aggregates are co-localized with a high frequency with Rnq1C-CFP and Sup35NM-CFP aggregates in the yeast cells containing [PIN+] and [PSI+] prions, and physical interaction of these aggregated proteins was confirmed by FRET. This is one of a few known cases of physical interaction of non-Q/N-rich amyloid-like protein and Q/N-rich amyloids, suggesting that interaction of different amyloid proteins may be determined not only by similarity of their primary structures but also by similarity of their secondary structures and of conformational folds.

EFFECT OF SOMEUNFAVORABLE FACTORS OF ENVIRONMENT ON THE SURVIVAL OF CHILDREN WITH ACUTE LEUKEMIA IN A LONG6TERM PERIOD AFTER ACCIDENT ON THE CHORNOBYL NPP. / VPLYV DEIaKYKh NESPRYIaTLYVYKh ChYNNYKIV DOVKILLIa NA VYZhYVANIST' DITEI Z GOSTRYMY LEIKEMIIaMY U VIDDALENYI PERIOD PISLIa AVARIÏ NA ChORNOBYL'S'KII AES.

OBJECTIVE: Determine of the influence of adverse environmental factors, including irradiation, on the survival ofchildren with acute leukemia in the long-term period after the Chornobyl accident (2008-2017). MATERIALS AND METHODS: Examined 74 children with acute leukemia (АL): 64 with acute lymphoblastic leukemia(ALL); 10 - acute myeloblastic leukemia (AML). The influence of negative environmental factors was assessed bythe degree of integrated pollution of the atmospheric air, surface waters and soils with pesticides, heavy metals (Pb,Cu, Ni, Cr, Mn, Zn, Fe) and cesium isotope 137Cs. These regions were ranked on a moderately polluted (1), polluted (2),very (3) and extremely (4) polluted territories. Took into account the age of children, blood test, immunophenotyp-ic of variant the acute leukemia, survival of patients and place of residence (city / village), serum ferritin level (SF). RESULTS: Exposure doses of children were in the range from 0.4 mSv to 35.0 mSv (average values were (4.25 ± 0.63 mSv)and did not affect the prognosis and variants of AL. 52 children lived in moderately and polluted territories (30 wereresidents of cities, 22 - villages). 22 patients were lived in very and extremely polluted territories (4 were residentsof cities, 18 - villages). Of 74 patients with ALL and AML 24 children died (32.4 %). The smallest number ofchildren, who died, were patients with «general type¼ В-ALL (18.7 %), most of all children with pro-В-ALL (8 out of10) and Т-ALL (3 of 4). Of the 52 patients, the inhabitants of moderately and polluted regions, 13 patients died (25%), while out of 22 patients, who lived in very and extremely polluted areas, 11 children died (50 % share)(rs = 0.39; p < 0.05). Of the 10 patients with AML, 4 children died. Most often, children died, who were residents ofvillages. Moreover, the level of SF was significantly higher in children over 6 years, the inhabitants of villages -(406.8 ± 40.6) ng/ml, compared to younger patients - (211.2 ± 32.1) ng/ml) and residents of of cities: up to 6years - (297.4 ± 52.3) ng/ml; over 6 years - (275.6 ± 29.8) ng/ml. CONCLUSIONS: The obtained data testify to the negative influence of environmental factors, including iron, and canbe the basis for understanding the mechanisms of potentiating influence of metals and their compounds on thedevelopment of malignant diseases of the blood system in children.

Association study of methylenetetrahydrofolate reductase genetic polymorphism 677C>T with schizophrenia in hospitalized patients in population of European Russia.

The purpose of the research was to investigate the association of methylenetetrahydrofolate reductase (hereinafter MTHFR) genetic polymorphism 677C>T with schizophrenia in the Russian population in comparison with the control group of healthy blood donors. Also some characteristics of schizophrenia were examined in patients with/without defective T-allele of MTHFR677C>T polymorphism. 500 patients with schizophrenia and 499 blood donors were examined for T-allele carriage of polymorphism MTHFR677C>T by PCR method. 150 archival medical records were studied (in the first patients included in the study). The carriage of T-allele of genetic polymorphism MTHFR677C>T was significantly more common in patients than in healthy donors: 255/500 versus 219/499 (p=0,0287, χ2=4,79; OR=1,33, 95%CI [1037; 1707]). The number of patients with chronic type of schizophrenia onset was significantly more among T-allele carriers (n=77) than among normal CC-genotype carriers (n=73): р=0.038. The number of "incapacitated" persons in the group of patients with defective T-allele (n=77) was significantly higher than in patients with normal genotype (n=73, p=0.0439; OR=2.878, 95%CI=1.111-7.456). The results suggest that T-allele of genetic polymorphism MTHFR677C>T in the population of European Russia may increase the risk of developing schizophrenia and its unfavorable prognosis, which requires further investigation.

[Biomarkers and mechanisms of early vascular damage]. / Biomarkery i mekhanizmy rannego povrezhdeniia sosudistoi stenki.

AIM: To assess the association of classic vascular risk factors, indicators of cerebral arteries wall damage and stress induction, and their role in early vascular and brain damage in middle age subjects without vascular events. MATERIAL AND METHODS: 87 patients were evaluated (49 women, 38 men, mean age 51.2±6.5). The following vascular risk factors were assessed: hypertension, diabetes, total cholesterol and low density lipoproteins levels, obesity and smoking. Patients underwent ultrasound of neck arteries, brain MRI and laboratory testing of blood parameters, probably associated with vascular wall damage: CRP, TNF-α, sICAM-1, sVCAM, HIF1-α, NO, VAP-1, VEGF-A, VEGF-C, sVEGF-R1, sVEGF-R2, TGF-ß1, general antioxidant status. RESULTS AND CONCLUSION: Mediating role of stress parameters in risk factors formation, initiation and maintenance of mechanisms of vascular damage was demonstrated. Hypercortisolemia suggested the association with age, atheromatosis, local inflammatory reactions via the TGF-ß1-HIF-1-VEGF family, systemic inflammation response via CRP, and elevated epinephrine levels were associated with TNF-α-mediated systemic inflammation. The association of TNF-α and MRI signs of cerebral small vessel disease (SVD) in non-hypertensive patients may indicate that TNF-α-mediated inflammation and increased permeability of vessel wall is an independent cause and potential biomarker of early small vessel damage. Influence of hypertension on age-dependent SVD is probably maintained by local vascular wall damage mechanisms via the TGF-ß1-HIF-1-VEGF family. However, hypertension heterogeneity and association of early cerebral vessels damage with various protective reactions require further clarification of the conditions for using these parameters as possible biomarkers of early SVD.

Cortisol level as risk factor for malignant hematologic pathology in children exposed to ionizing radiation after Chornobyl accident. / STAN ERYTROÏDNOÏ, GRANULOTsYTARNOÏ TA TROMBOTsYTARNOÏ LANOK GEMOPOEZU NA ETAPAKh KhIMIOTERAPIÏ U DITEY̆ Z GOSTRYMY LIMFOBLASTNYMY LEY̆KEMIIaMY, IaKI ZAZNALY VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: Determination of serum cortisol level in the initial period of acute leukemia in children, who exposed to ion izing radiation and other factors of Chornobyl accident, depending on their age and prognosis of disease. MATERIALS AND METHODS: The study involved 283 children residents of Kyiv, Zhytomyr and Chernihiv regions. There were 90 acute leukemia patients(AL) (ALL - 56, AML - 34), and 193 people of comparison group with anemia, leukemoid reactions and lymphadenopathy. We analyzed the type of comorbid somatic pathology, diseases in the genealogy, hematological parameters, cortisol levels in blood serum and irradiation doses in all children. In patients with AL expected median survival was calculated. RESULTS: In 28.9 % of AL children the initial cortisol content was below 200 nmol/l, in 7.8 % - higher than 500 nmol/l (in the comparison group 10.4 % and 17.1 % respectively). Among AL patients with cortisol levels below 200 nmol/l were significantly less amount of persons with chronic bacterial infections and persistent viral infections (CMV, EBV) and in the genealogy of these children allergic reactions, endocrine pathology diagnosed more often compared with patients, whose hormone levels was higher than 200 nmol/l (p < 0.05). Distribution of children from control group by gradations of cortisol, age groups, defined somatic pathology and diseases in genealogy had no difference. It is shown, that lower initial blood serum cortisol level in ALL children correlates to a greater probability of relapse (Rs = -0,67). In patients with AML a direct correlation between cortisol level and median survival was detected (Rs = 0,79). Children radiation doses were ranging from 0.08 mSv to 14.9 mSv, and there were slightly higher among residents of Zhytomyr region (8.4 ± 1.2 mSv) compared to other regions. However, these doses did not affect blood serum cortisol levels in children and the course of AL. CONCLUSIONS: These data suggest the need for correction and individualization of corticosteroid doses for optimization of AL patients treatment. Children, who have lower than normative serum cortisol levels are at increased risk of hema tologic pathology and they need for hematologic monitoring.

Activity of 8F4, a T-cell receptor-like anti-PR1/HLA-A2 antibody, against primary human AML in vivo.

The PR1 peptide, derived from the leukemia-associated antigens proteinase 3 and neutrophil elastase, is overexpressed on HLA-A2 in acute myeloid leukemia (AML). We developed a high-affinity T-cell receptor-like murine monoclonal antibody, 8F4, that binds to the PR1/HLA-A2 complex, mediates lysis of AML and inhibits leukemia colony formation. Here, we explored whether 8F4 was active in vivo against chemotherapy-resistant AML, including secondary AML. In a screening model, coincubation of AML with 8F4 ex vivo prevented engraftment of all tested AML subtypes in immunodeficient NSG (NOD scid IL-2 receptor γ-chain knockout) mice. In a treatment model of established human AML, administration of 8F4 significantly reduced or eliminated AML xenografts and extended survival compared with isotype antibody-treated mice. Moreover, in secondary transfer experiments, mice inoculated with bone marrow from 8F4-treated mice showed no evidence of AML engraftment, supporting the possible activity of 8F4 against the subset of AML with self-renewing potential. Our data provide evidence that 8F4 antibody is highly active in AML, including chemotherapy-resistant disease, supporting its potential use as a therapeutic agent in patients with AML.

[Psychopathological characteristics and social functioning of the schizophrenic patients with the T allele of the MTHFR677C>T polymorphism]. / Psikhopatologicheskaya kharakteristika i osobennosti sotsial'nogo funktsionirovaniya bol'nykh shizofreniei s nositel'stvom T-allelya v polimorfnom lokuse gena obmena folatov MTHFR677C>T.

AIM: To compare the severity of psychopathological symptoms and characteristics of personal and social functioning in patients with schizophrenia, carriers of different alleles of the MTHFR677C>T polymorphism. MATERIAL AND METHODS: One hundred and fifty patients diagnosed with schizophrenia were genotyped for the MTHFR677C>T polymorphism, some of them were examined using psychometric scales and tests (PANSS, SANS, PSP, CDSS, a battery of cognitive tests etc). RESULTS AND CONCLUSION: Patients with the MTHFR677T variant had greater severity of negative symptoms regardless of psychometric instruments used in the study, greater severity of schizophrenia disorder in whole measured with the PANSS General psychopathological symptoms subscale, higher scores on the PANSS cognitive cluster and lower levels of personal and social functioning measured with the PSP compared to the patients with the MTHFR677CС genotype. The results of psychometric testing are in line with significant differences of MTHFR677T allele carriers from those with the MTHFR677CС genotype in the number of disable patients and the use of different types of psychiatric services. The differences were not related to sex, age, illness duration and depressive symptoms measured with CDSS and PANSS «depression/anxiety¼ factor.

[Comparative, placebo-controlled clinical study of efficacy and safety of glatiramer acetate 20 mg in patients with relapsing-remitting multiple sclerosis: results of the first year of the study]. / Sravnitel'noe platsebo-kontroliruemoe klinicheskoe issledovanie effektivnosti i bezopasnosti preparatov glatiramera atsetata 20 mg u patsientov s remittiruyushchim rasseyannym sklerozom: rezul'taty pervogo goda nablyudeniya.

The article presents the results of international multicenter randomized double-blind, active and placebo-controlled, comparative phase 3 trial. The goal of the study was to demonstrate non-inferiority of BCD-063 (glatiramer acetate, manufactured by JSC «BIOCAD¼, Russia) to copaxone-Teva (Teva Pharmaceutical Enterprise Co., Ltd., Israel) in patients with relapsing-remitting multiple sclerosis. METHODS: 158 patients with relapsing-remitting multiple sclerosis were randomly assigned into 3 groups: BCD-063, copaxone-Teva and placebo, at a ratio of 2:2:1, respectively. RESULTS AND CONCLUSION: Efficacy analysis after 48 weeks of therapy demonstrated no differences between BCD-063 group and copaxone-Teva group in both MRI parameters and frequency of relapses. The mean (SD) of number of MRI-confirmed relapses per patient per year (the primary endpoint) in BCD-063 group was 0.098361 (0.351422), in copaxone-Teva group - 0.098361 (0, 351 422) and in placebo group - 0.178571 (0.390021). There were also no differences between the groups for all other efficacy parameters (EDSS and MSFC). Both investigational BCD-063 and copaxone-Teva demonstrated a favorable safety profile. The data obtained from the present study confirm the therapeutic equivalence of BCD-063 (CJSC BIOCAD, Russia) and copaxone-Teva, that is important for further implementation of glatiramer acetate generic in the clinical practice of multiple sclerosis therapy.

[Hereditary afibrinogenemia: A literature review and clinical observations]. / Nasledstvennaia afibrinogenemiia: obzor literatury i klinicheskie nabliudeniia.

Afibrinogenemia is a rare congenital coagulopathy that leads to life-threatening bleeding. In afibrinogenemia, plasma fibrinogen levels are less than 0.1 g/L. The clinical manifestations of the disease can be both bleeding and thromboses of different localizations, which is determined by the multifunctional role of fibrinogen in hemostasis. The described cases demonstrate different clinical phenotypes of the disease. In both cases the diagnosis was confirmed by genetic examinations that revealed homozygous mutations in the fibrinogen A genes. The nature of the mutations assumes consanguineous marriages, as confirmed by the results of a genealogical analysis. Fibrinogen preparations are promising in treating afibrinogenemia in Russia.

Modern state of problem of delivery of medicines with use of erythrocytes as cell-carriers.

Erythrocytes are prospective carriers of wide range of medicines and other biologically active agents. Main peculiarity and advantage of erythrocytes as carriers of medicines is their absolute bio-compatibility and ability for long circulation in an organism. While growing old these cells undergo natural process of biodegradation. Relatively inactive endocellular environment protects carried medicine from being inactivated by different endogenous factors. At the present time different methods of loading medicines in erythrocytes are used: electroporation, induced endocytosis, osmotic pulse hematolysis, hypotonic hematolysis. Most of these methods are based on the ability of these cells for reversible deformation of the surface without changing area of surface. Introduction of medicines in erythrocytes can be conducted in natural way as a result of their sorption on cell membrane. Different medicines can be used as the objects for targeted transport: antibiotics, antineoplastic drugs, corticosteroids, peptides, enzymes etc. extracorporeal pharmacotherapy with use of erythrocytes as carriers can be applied in the treatment of different diseases. Range of used medicines and provided possibilities is quite wide at a present time, but further development of this direction is very prospective. The aim of the authors was to outline a common concept of the potential of erythrocytes as universal transportation means of medicines for therapy of different pathological conditions.

[Atherogenesis in human - clinical aspects of circulating immune complexes].

It has been suggested that circulating immune complexes containing low density lipoproteins (LDL-CIC) play a role in atherogenesis and are involved in the formation of early atherosclerotic lesions. The complexes, as well as anti-LDL antibody were found in the blood of patients with atherosclerotic process in various cardiovascular diseases, well as in the blood of animals with experimentally modulated atherosclerosis. One can assume that the presence anti-LDL antibodies in blood is a result of an immune response that is induced by modification of lipoproteins. LDL-CIC differ from native LDL in many aspects. They have much lower levels of sialic acid, a smaller diameter and a higher density electronegativity than native LDL. The fraction of the LDL-CIC in serum is an important manifestation of the atherosclerotic process. LDL-CIC, unlike the native LDL is able to induce intracellular accumulation of neutral lipids, especially esterified cholesterol in cell cultures obtained from healthy human aortic intima and macrophages in culture. After removal of the LDL-CIC, the serum of CHD-patients loses its atherogenic properties. The titer of the LDL-CIC in the blood serum significantly correlate with the progression of atherosclerosis and in vivo has the highest diagnostic yield of measured among other lipid parameters. Increasing CIC- cholesterol could also increase the risk of coronary artery atherosclerosis.

[Structural and Functional Properties of Vascular Endothelium].

We have summarized in this paper main conceptions on structure and function of vascular endothelium with special attention to the role of caveolae both in regulation of function of endothelium itself and transvesicular transport of metabolic substrates. We have also described the role of shear stress in activation of vascular endothelium and putative mechanisms of its action.

[Structural and Functional Properties of Vascular Endothelium].

We have summarized in this paper main conceptions on structure and function of vascular endothelium with special attention to the role of caveolae both in regulation of function of endothelium itself and transvesicular transport of metabolic substrates. We have also described the role of shear stress in activation of vascular endothelium and putative mechanisms of its action.

[Prognostication of immunological reactivity and the choice of the variant of reflexotherapy for a newborn infant].

AIM: The objective of the present study was to determine the classification differences in immunological reactivity and to identify its predictors in the newborn infants. MATERIAL AND METHODS: The study involved 115 full-term newborn infants presenting with grade 3 prenatal hypoxic ischemic encephalopathy in the late neonatal period. The features of immunological reactivity under the influence of acupuncture were examined. Statistical processing was carried out by means of discriminant analysis. RESULTS: The assessment and prediction of the effectiveness of acupuncture in the neonates suffering from cerebral ischemia are based on the index of immunological reactivity and the leukocyte index of intoxication, as well as on the ratio of monocytes to band neutrophils content. For generation of the group classifier of immunological predictors in a newborn infant and development of indications for reflex therapy, nine parameters of interest were measured. The group specificity of the child was determined by three variables, viz. leukocyte index of intoxication, monocyte and band neutrophil counts with values of the Fisher's exact test (F) and reliability (Wilks Lambda 0.90894; approximation F (3.144) = 4.809; p < 0.0032). The partial Wilks Lambda values showed that the greatest contribution was provided by the leukocyte index of intoxication and monocytes. Prediction accuracy of the classification matrix in the standard treatment group reached 30.8% and 91.7% respectively when reflex therapy was included in the combined rehabilitation treatment. Overall, classification accuracy amounted to 70.3%. The presence of distinctive changes in the subgroups preconditioned a personalized approach to the prescription of reflex therapy to the newborn infants and the choice of the treatment modality on an individual basis (parent, child, or both) in the "mother-newborn" system. The variant of treatment was determined by comparing the values of the results of the formulas. The newborns were referred to the subgroup with the highest value of the classification function. The predictors made it possible to reliably distinguished the second (p = 0.032) and the third (p = 0.022) subgroups from the first one, with some degree of overlapping between the edge zones of centroids of the second and third subgroups (p = 0.073). Therefore, the sensitivity of classification in the individual subgroups was lower than in the group model and was estimated at 34.4, 71.9, and 65.6% for the first, second and third groups, respectively. CONCLUSION: The mathematical models can discriminatebetween the immunological characteristics and predict them in individual newborn infants; also, they can be helpful for preventing the disruption of their adaptation process.

[Use of anti-B-cell therapy in case of antisynthetase syndrome as the severest subtype of polymyositis/dermatomyositis].

Antisynthetase syndrome encompassing a symptom complex with severe interstitial lung disease is the severest subtype of polymyositis and dermatomyositis. The characteristic feature of antisynthetase syndrome is the insufficient efficiency of traditional therapy with glucocorticosteroids and cytostatics, which determines the prognosis of the disease and the need for new therapeutic approaches to treating these patients.

Super-rogue waves in simulations based on weakly nonlinear and fully nonlinear hydrodynamic equations.

The rogue wave solutions (rational multibreathers) of the nonlinear Schrödinger equation (NLS) are tested in numerical simulations of weakly nonlinear and fully nonlinear hydrodynamic equations. Only the lowest order solutions from 1 to 5 are considered. A higher accuracy of wave propagation in space is reached using the modified NLS equation, also known as the Dysthe equation. This numerical modeling allowed us to directly compare simulations with recent results of laboratory measurements in Chabchoub et al. [Phys. Rev. E 86, 056601 (2012)]. In order to achieve even higher physical accuracy, we employed fully nonlinear simulations of potential Euler equations. These simulations provided us with basic characteristics of long time evolution of rational solutions of the NLS equation in the case of near-breaking conditions. The analytic NLS solutions are found to describe the actual wave dynamics of steep waves reasonably well.

Quantitative aspects of RNA silencing in metazoans.

Small regulatory RNAs (microRNAs, siRNAs, and piRNAs) exhibit several unique features that clearly distinguish them from other known gene regulators. Their genomic organization, mode of action, and proposed biological functions raise specific questions. In this review, we focus on the quantitative aspect of small regulatory RNA biology. The original nature of these small RNAs accelerated the development of novel detection techniques and improved statistical methods and promoted new concepts that may unexpectedly generalize to other gene regulators. Quantification of natural phenomena is at the core of scientific practice, and the unique challenges raised by small regulatory RNAs have prompted many creative innovations by the scientific community.

[Recombinant activated factor VII use for the bleeding implications prevention during central venous catheterization in pediatric patients with acute leucosis and thrombocytopenia].

UNLABELLED: Research objective was to develop an algorithm of the recombinant activated Factor VII (rFVIIa) prophylactic use for the bleeding implications prevention during central venous catheterization in Pediatric patients with acute leucosis and thrombocytopenia. METHODS: 30 Pediatric patients with acute leucosis and thrombocytopenia received rFVIIa 30-120 microg kg(-1) before the internal jugular vein catheterization with ultrasound control. Comparative group 1 included 39 Pediatric patients without preventive haemostatic treatment; comparative group 2 included 30 patients received platelet concentrate. RESULTS: the first attempt catheterization numbers increased, the time of the catheterization was reduced, platelet aggregation was improved and the bleeding implications frequency was 6.6% in patients received rFVIIa before the internal jugular vein catheterization. 23.1%--in the comparative group 1; 26.7% in the comparative group 2. CONCLUSION: Ultrasound navigation and rFVIIa preventive use together improve internal jugular vein catheterization results.