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Nedelcheva Simona Ivanovska Sofiya Durchova Mariya Koprinkova-Hristova Petia 《Cluster computing》2022,25(3):1637-1644
Cluster Computing - The paper presents a supercomputer parallel implementation of a brain inspired model combining a Python module simulating a layer of retina ganglion cells and NEST Simulator for... 相似文献
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K M Smits L Gaspari M P Weijenberg V Dolzan K Golka H C Roemer V Nedelcheva Kristensen M C Lechner G I Mehling J Seidegard R C Strange E Taioli 《Biomarkers》2003,8(3-4):299-310
Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-mu (GST-mu). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-mu enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (chi2=0.007, p=0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype 相似文献
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Batovska DI Todorova IT Nedelcheva DV Parushev SP Atanassov AI Hvarleva TD Djakova GJ Bankova VS Popov SS 《Journal of plant physiology》2008,165(8):791-795
We examined the leaf chemical composition of six seedlings obtained by self-pollination of the Bulgarian wine-making variety Storgozia as well as the cultivar Bouquet, which is the susceptible parent of Storgozia. The chemical composition was investigated in the framework of a program for identification of metabolites associated with disease resistance in grape-vine. Acetone, dichloromethane and butanol extracts, as well as volatiles obtained from fresh material were analyzed by GC/MS. Based on the correlations of the GC/MS data and estimated resistance of the leaves towards the etiological agents of powdery mildew, downy mildew and botrytis as biomarkers for the fungal resistance, we proposed 16 individual metabolites – - and γ-tocopherol, squalene, -amyrine, stigmasta-3,5-diene-7-one, hexahydrofarnesyl acetone, glycolic acid, 3-hydroxybutanoic acid, 3-hydroxycaproic acid, malic acid, tartaric acid, erythronic acid, arabinoic acid, monoethyl phosphate, undecyl laurate and isopropyl myristate. The obtained correlations were confirmed by cluster analysis. 相似文献
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Sonya?Dimitrova?Uzunova Alexander?Stefanov?Zarkov Anna?Marianova?Ivanova Stoyno?Stefanov?Stoynov Marina?Nedelcheva?Nedelcheva-VelevaEmail author 《Cell division》2014,9(1):4
Background
The S-phase checkpoint aims to prevent cells from generation of extensive single-stranded DNA that predisposes to genome instability. The S. cerevisiae complex Tof1/Csm3/Mrc1 acts to restrain the replicative MCM helicase when DNA synthesis is prohibited. Keeping the replication machinery intact allows restart of the replication fork when the block is relieved. Although the subunits of the Tof1/Csm3/Mrc1 complex are well studied, the impact of every single subunit on the triple complex formation and function needs to be established.Findings
This work studies the cellular localization and the chromatin binding of GFP-tagged subunits when the complex is intact and when a subunit is missing. We demonstrate that the complex is formed in cell nucleus, not the cytoplasm, as Tof1, Csm3 and Mrc1 enter the nucleus independently from one another. Via in situ chromatin binding assay we show that a Tof1-Csm3 dimer formation and chromatin binding is required to ensure the attachment of Mrc1 to chromatin. Our study indicates that the translocation into the nucleus is not the process to regulate the timing of chromatin association of Mrc1. We also studied the nuclear behavior of Mrc1 subunit in the process of adaptation to the presence hydroxyurea. Our results indicate that after prolonged HU incubation, cells bypass the S-phase checkpoint and proceed throughout the cell cycle. This process is accompanied by Mrc1 chromatin detachment and Rad53 dephosphorylation.Conclusions
In S. cerevisiae the subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3 independently enter the cell nucleus, where a Tof1-Csm3 dimer is formed to ensure the chromatin binding of Mrc1 and favor DNA replication and S-phase checkpoint fork arrest. In the process of adaptation to the presence of hydroxyurea Mrc1 is detached from chromatin and Rad53 checkpoint activity is diminished in order to allow S-phase checkpoint escape and completion of the cell cycle.6.
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Nedelcheva MN Roguev A Dolapchiev LB Shevchenko A Taskov HB Shevchenko A Stewart AF Stoynov SS 《Journal of molecular biology》2005,347(3):509-521
The replicative DNA helicases can unwind DNA in the absence of polymerase activity in vitro. In contrast, replicative unwinding is coupled with DNA synthesis in vivo. The temperature-sensitive yeast polymerase alpha/primase mutants cdc17-1, pri2-1 and pri1-m4, which fail to execute the early step of DNA replication, have been used to investigate the interaction between replicative unwinding and DNA synthesis in vivo. We report that some of the plasmid molecules in these mutant strains became extensively negatively supercoiled when DNA synthesis is prevented. In contrast, additional negative supercoiling was not detected during formation of DNA initiation complex or hydroxyurea replication fork arrest. Together, these results indicate that the extensive negative supercoiling of DNA is a result of replicative unwinding, which is not followed by DNA synthesis. The limited number of unwound plasmid molecules and synthetic lethality of polymerase alpha or primase with checkpoint mutants suggest a checkpoint regulation of the replicative unwinding. In concordance with this suggestion, we found that the Tof1/Csm3/Mrc1 checkpoint complex interacts directly with the MCM helicase during both replication fork progression and when the replication fork is stalled. 相似文献
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Kristensen VN Sørlie T Geisler J Yoshimura N Linegjaerde OC Glad I Frigessi A Harada N Lønning PE Børresen-Dale AL 《The Journal of steroid biochemistry and molecular biology》2005,95(1-5):105-111
Intratumoral levels of E1 (oestrone), E1S (oestrone sulphate) and E2 (oestradiol) are significantly reduced by treatment with the aromatase inhibitor anastrozole regardless of treatment response. The purpose of the present pilot study was to look for additional markers of biochemical response to aromatase inhibitors on mRNA expression level. Whole genome expression was studied using microarray analysis of breast cancer tissue from 12 patients with locally advanced tumors, both before and following 15 weeks of treatment with the aromatase inhibitor anastrozole (Arimidex®). Intratumoral mRNA levels for a subset of genes coding for steroid metabolizing enzymes, hormone receptors and some growth mediators involved in cell cycle control were analysed by quantitative RT-PCR. There was a correlation between the two methods for some but not all genes. The mRNA expression levels of the different genes were correlated to each other and to the intratumoral levels of E1, E2 and E1S, before and after the treatment. Notably, a correlation of the E1/E2 metabolic ratio to the mRNA levels of CYP19A1 was observed before treatment (r = 0.745, p < 0.005). Whole genome expression analysis of these 12 breast cancer patients revealed similar tumor classification to previously published larger studies. Tumors with no or low expression of ESR1 (oestrogen receptor) clustered together and were characterized by a strong basal-like signature highly expressing keratins 5/17, cadherin 3, frizzled and apolipoprotein D, among others. The luminal epithelial tumor cluster, on the other hand, highly expressed ESR1, GATA binding protein 3 and N-acetyl transferase. An evident ERBB2 cluster was observed due to the marked over-expression of the ERBB2 gene and GRB7 and PPARBP in this patient material). Using significance analysis of microarrays (SAM), we identified 298 genes significantly differently expressed between the partial response and progressive disease groups. 相似文献
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Katya Gabrovska Teodora Nedelcheva Tzonka Godjevargova Olya Stoilova Nevena Manolova Iliya Rashkov 《Journal of Molecular Catalysis .B, Enzymatic》2008,55(3-4):169-176
The three new dual-layer matrices (polyacrylonitrile (PAN) membranes coated with physically bound chitosan (CHI)—PANCHI-A and chemically bound chitosan—PANCHI-B and PANCHI-C) for immobilization of acetylcholinesterase (AChE) were obtained. The chemical-modified PAN membrane (PAN-NaOH + ethylenediamine (EDA)) was used as a base for the prepared dual-layer membranes. For chemical chitosan bound membrane, chitosan was tethered onto the membrane surface to form a dual-layer biomimetic membrane in the presence of glutaraldehyde (GA). The basic characteristics (amount of amino groups, hydrophilicity and transport characteristics) of the chitosan-modified membranes were investigated. The SEM analyses were shown essential morphology change in the different chitosan membranes.The relative activities and Vmax of the covalently immobilized enzyme on PANCHI-B and PANCHI-C membranes were higher than that on PANCHI-A membrane and chemical-modified membrane with NaOH + EDA. Km values for the different modified membranes are lower for the chitosan-treated membranes. The pH and temperature optimum of immobilized enzyme were determined. The bound enzymes on PANCHI-B and PANCHI-C have higher thermal and storage stability in comparison with AChE on PANCHI-A membrane and free enzyme. 相似文献
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Nechev J Stefanov K Nedelcheva D Popov S 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2007,146(4):568-575
The compositions of the volatile and polar fractions from two coexisting Black Sea invertebrates, the mussel Mytilus galloprovincialis and the beadlet anemone Actinia equina, were established. The main metabolites in the volatile fraction from the investigated animals appeared to be methyl esters of fatty acids and fatty aldehydes. In the polar fraction from both animals low concentrations of free acids and nitrogen-containing compounds were obtained. Free carbohydrates were in much higher concentrations in M. galloprovincialis than in A. equina. Some sterols, probably as polar conjugates, were identified mainly in A. equina. Significant changes among all compounds appeared after treatment of both invertebrates with two different concentrations of cobalt ions. The variety of changes in each invertebrate could be due to their different evolutionary status. The effect of cobalt ions was often stronger at medium cobalt-ion concentrations. 相似文献