Theoretical Models for Quantitative Description of the Acid-Base Equilibria of the 5,6-Substituted Uracils.

The acidities of 18 5,6-substituted uracils have been numerically estimated as pK values in terms of three theoretical models. The first scheme includes the calculation of the gas-phase acidity of uracil with the G3MP2B3 method and taking into account the solvent effect using the polarizable continuum approximation PCM(SMD)-TPSS/aug-cc-pVTZ. The second model is one step and implies calculation of the free Gibbs energies of the hydrate complex of uracil (and its anion) with 5 water molecules by the TPSS/aug-cc-pVTZ method.

Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder.

Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci.

Dependence of growth inhibiting action of increased planting density on capacity of lettuce plants to synthesize ABA.

Inhibition of lettuce plant growth under increased planting density was accompanied by accumulation of abscisic acid (ABA) in the shoots of competing plants. To check causal relationship between these responses we studied the effect of decreased synthesis of ABA on growth indexes and hormonal balance of lettuce plants under elevated density of their planting (one (single) or three (competing) plants per pot). Herbicide fluridone was used to inhibit ABA synthesis.

Controlled stabilization of anionic forms of the uracil derivatives: A DFT study.

Relative stabilities of the N1/N3/О5/О6 anions of 42 substituted uracils in gas phase and aqueous solutions have been theoretically studied using approximation IEFPCM (SMD) - TPSS/aug-cc-pVTZ. The specific solvation of uracil and its anions has been simulated with the first hydrate shell made up with 5 water molecules. The nonspecific solvation has been accounted in terms of the SMD model.

Effects of Bacillus subtilis on some physiological and biochemical parameters of Triticum aestivum L. (wheat) under salinity.

Endophytic strain Bacillus subtilis (B. subtilis) 10-4, producing indole-3-acetic acid (IAA) and siderofores but not active in phosphate solubilization, exerted a protective effect on Triticum aestivum L. (wheat) plant grown under salinity (2% NaCl) stress.

Association analysis identifies 65 new breast cancer risk loci.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry.

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 with ten variants at nine new loci.

[The role of interactions of transposons with epigenetic factors in the aging process].

The review considers modern theories of aging mechanisms and data on epigenetic regulation of ontogenesis. Transposons may be the material bases of the epigenetic control system, their movements affect the differentiation of cells and can cause genomic instability. Control systems aimed at protecting against foreign DNA (splicing machine, microRNA processing) became the basis of regulatory networks of genomes underlying cell differentiation.

Microstructure changes in ultrafine-grained nickel processed by high pressure torsion under ultrasonic treatment.

Commercially pure nickel was processed by high pressure torsion (HPT) and subjected to ultrasonic treatment (UST) with different amplitudes of compression-tension stresses in the zone of stress antinode of a standing wave. It was found that microstructure parameters such as the dislocation density, low- and high-angle grain boundary fractions, microhardness, and the stored excess energy as well, non-monotonically depend on the ultrasound amplitude. A structure relaxation leading to a reduction of internal stresses and stored energy and increase of the fraction of high-angle boundaries was observed at some intermediate amplitudes of the oscillating stress.

Anti-Inflammatory Activity of Novel 12-N-methylcytisine Derivatives.

Background And Objectives: Neurodegenerative diseases and inflammation are always linked to each other; therefore the elaboration of new chemical compounds, which interact with pharmacological targets involved into these two processes, can become one of ways of correction of these types of human CNS pathology. In the field of this problem the anti-inflammatory activity of ten 3-amino derivatives of quinolizidine alkaloid (.)-cytisine (the data about nootropic activity of these compounds are outlined by us previously) was studied by using in vivo, in vitro and in silico approaches.

A graphic approach to the analysis of a large X-ray microanalysis dataset obtained via SEM-EDS.

A graphical method for phase analysis of advanced materials by EDS-SEM was developed and demonstrated on deformed superconducting Bi(Pb)2223 ceramics. Through visual representation, this method allows for the rapid and efficient analysis of large X-ray microanalysis datasets and to identify phase composition of fine particles of secondary phases against a background of other phases. The graphical method can be applied using existing software and therefore does not require the development of new programs or complex computations.

Origin and spread of human mitochondrial DNA haplogroup U7.

Human mitochondrial DNA haplogroup U is among the initial maternal founders in Southwest Asia and Europe and one that best indicates matrilineal genetic continuity between late Pleistocene hunter-gatherer groups and present-day populations of Europe. While most haplogroup U subclades are older than 30 thousand years, the comparatively recent coalescence time of the extant variation of haplogroup U7 (~16-19 thousand years ago) suggests that its current distribution is the consequence of more recent dispersal events, despite its wide geographical range across Europe, the Near East and South Asia. Here we report 267 new U7 mitogenomes that - analysed alongside 100 published ones - enable us to discern at least two distinct temporal phases of dispersal, both of which most likely emanated from the Near East.

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.

Opinions of hearing parents about the causes of hearing impairment of their children with biallelic GJB2 mutations.

Hereditary hearing impairment (HI) caused by recessive GJB2 mutations is a frequent sensory disorder. The results of the molecular-based studies of HI are widely used in various genetic test systems. However, the ethical aspects are less described than the genetic aspects.

[MicroRNAs as potential noninvasive markers in the diagnosis of urological malignancies].

Small non-coding RNAs (microRNAs) are involved in almost all biological mechanisms of carcinogenesis. Due to their stability in biological fluids microRNAs may serve a perspective biomarker for diagnosis and prognosis of oncological diseases. The review is dedicated to the analysis of microRNAs, as potential diagnostic markers of urological malignancies.

Enhancing 4-propylheptane dissociation with nickel nanocluster based on molecular dynamics simulations.

In the present work, a 0.4nm nickel cluster has been theoretically studied. Its equilibrium structural parameters have been calculated by the DFT method based on the PBEH1PBE hybrid functional and split-valence basis set Lanl2DZ including effective core potentials.

Assessment of an APOBEC3B truncating mutation, c.783delG, in patients with breast cancer.

Purpose: APOBEC3B belongs to the family of DNA-editing enzymes. A copy number variant targeting the genomic APOBEC3A-APOBEC3B locus has a significant impact on breast cancer risk, but the relative contribution of APOBEC3B is uncertain. In this study, we investigate a loss-of-function mutation that selectively targets APOBEC3B, for its association with breast cancer risk.

Expression profiles and hormonal regulation of tobacco NtEXGT gene and its involvement in abiotic stress response.

Despite the intensive study of xyloglucan endotransglucosylases/hydrolases, their multifaceted role in plant growth regulation in changing environmental conditions is not yet clarified. The functional role of the large number of genes encoding this group of enzymes is also still unclear. NtEXGT gene encodes one of xyloglucan endotransglucosylases/hydrolases (XTHs) of Nicotiana tabacum L.

Structural Organization of Cerebral Basolateral Nucleus of the Amygdaloid Complex in WAG-Rij Rats with Different Genotypes by the TAQ 1A Locus of Dopamine 2 Receptor Gene (DRD2).

Anxiety levels and structural organization of the basolateral nucleus of the amygdaloid complex were analyzed in WAG/Rij rats with genotypes A/A and A/A by DRD2 locus Taq 1A. Association of anxious behavior with A/A genotype and the relationship between the structural organization of the nucleus and polymorphic variants of this locus are detected.

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk.

Purpose: CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC).

The Simons Genome Diversity Project: 300 genomes from 142 diverse populations.

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome.

Genomic analyses inform on migration events during the peopling of Eurasia.

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets.

A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics.

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes.

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.

Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.