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Zakharenko AL Sukhanova MV Khodyreva SN Novikov FN Stroĭlov VS Nilov DK Chilov GG Shviadas VK Lavrik OI 《Molekuliarnaia biologiia》2011,45(3):565-569
A search for poly(ADP-ribose) polymerase-1 inhibitors by virtual screening of a chemical compound database and a subsequent experimental verification of their activities have been done. It was shown that the most efficient method to predict inhibitory properties implies a combinatorial approach joining molecular docking capabilities with structural filtration. Among more than 300000 database chemicals 9 PARP1 inhibitors were revealed; the most active ones, namely: STK031481, STK056130, and STK265022,--displayed biological effect at a micro-molar concentration (IC50 = 2.0 microM, 1.0 microM and 2.6 microM, respectively). 相似文献
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Microsporidia is a large group of fungi-related unicellular eukaryotes with obligate intracellular lifestyle infecting a wide range of invertebrate and vertebrate hosts. Long adaptation of the parasites to intracellular development resulted in extraordinary minimization of their metabolic system. The paper summarizes the original results and literature data on the study of microsporidian carbohydrate and energy metabolism. On the basis of the material, it is concluded that minimization of microsporidian cell machinery was accompanied by the acquisition of a number of unique characteristics, which were not found in other eukaryotes. 相似文献
996.
Liskovykh MA Chuĭkin IA Ranjan A Safina DA Tolkunova EN Minina IuM Zhdanova NS Dyban PA Mullins J Kostyleva EI Chikhirzhina EV Bader M Alenina N Tomilin AN 《Tsitologiia》2011,53(12):939-945
The rat represents very important, superior in many respects to the mous, animal model for studying pharmacology, physiology, ageing, cardiovascular etc. However, numerous attempts to derive rat ES cells necessary to carry out loss-of-gene-function studies have not been successful thus far. Therefore rat induct pluripotent stem cells (or riPS) should provide a notable alternative to ES cell, allowing to study gene functions in this valuable animal model. Here we report an improved lentivirus-based riPS derivation protocol that makes use of small inhibitors of MEK and GSK3. We show that the excision of proviruses does not affect neither karyotype and pluripotency state of these cells. Also, we propose genetic tool for an improvement of the quality of riPS cells in culture. These data may prompt further iPS-based gene targeting in rat as well as the development iPS-based gene therapies, using this animal model. 相似文献
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Korobeĭnikova II 《Fiziologiia cheloveka》2011,37(5):26-34
Examinees, which consisted of 46 young males, were offered to memorize and recreate a sequence of signals on a computer monitor. These signals were to be recreated in regard to the original sequence and location. Examinees were divided into two groups depending on their degree of approximation of the correct location of the signal sequence. The first group, unlike the second (in contrast to the second one), had a very high rate of accuracy with the least number of mistakes. EEG reading was taken on the examinees prior to completing the test, during the memorization stage and during the completion of task. The EEG reading taken prior to the test and those of the completion of task showed no difference in the range ofteta rhythm for both groups of examinees. However, during the memorization stage, the examinees of the first group, unlike that of the second, showed an increase in the coefficient of proximity in the line of teta rhythm EEG of the right hemisphere of the brain. Three systems of connection with the focuses of activity in the right rear, right center and right front areas of the brain, in which the proximity of teta range of EEG during the memorization stage, were noticeably higher in the group of examines that showed high accuracy during the primary attempts of recreation of the sequence. Since the right hemisphere deals mainly with spatial perception of the information and is more active at processing of nonverbal and stereotyped signals, we suggest that students belonging to different groups employed different strategies of processing of the task during remembering. 相似文献
1000.
Vakhitova IuV Antipina EI Yamidanov RS Khisamutdinova RIu Zarudiĭ FS Baschenko NZh Dokichev VA Tomilov IuV Nefedov OM 《Bioorganicheskaia khimiia》2011,37(6):821-829
The goal of the current work is to study the molecular mechanisms underlay the action of 5- amino-exo-3-azatricyclo[5.2.1.0(2,6)]decan-4-one (P-11) with combined antiarrhythmic, nootropic, anti-inflammatory and anaesthetic activities. The aconitine-induced experimental rat model of cardiac arrhythmia has been used in our study. Aconitine was administered once intravenously in a dose 50 microg/kg whereas experimental animal group received P-11 in a dose 0.3 mg/kg (the compound was injected intravenously 2 min before acute aconitine treatment). Expression macroarray (Atlas Rat cDNA Expression Array, #7738-1; BD Biosciences) was used to identify the target genes for P-11 compound. Comparative analysis of changes in the status of expression of genes in the heart of rats induced by P-11 against the simulated in vivo arrhythmia identified 16 genes that reproducibly alter the level of expression.These genes encode the extracellular matrix proteins (glypican 1, Gpc1; tissue inhibitor of metalloproteinase 2, 3, Timp2, Timp 3); intracellular signaling molecules (rho GTPase activating protein 7, Dlc1; protein tyrosine phosphatase 4a1, Ptp4a1; phosphodiesterase 4D, PDE4D; PI3-kinase regulatory subunit alpha, PIK3R1; guanine nucleotide binding protein alpha 12, Gna12) and protein of intermediate junctions (junction plakoglobin, Jup), proteins involved in glycolysis (phosphofructokinase I, Pfk1) and hemostasis (tissue plasminogen activator, Plat), plasma membrane transporters (Solute carrier family 16, member 1, Slc16a1; ATPase, Na+/K+ transporting, Atp1a), and ets. (c-fos protooncogene, c-fos; telomerase protein component 1, tlp; Annexin 1, anxa 1). Thus, the data about the selective effect of P-11 on genes whose products are involved in the aritmogenesys mechanisms, allow us to consider this compound as a promising means of pathogenetically oriented pharmacotherapy of cardiac arrhythmias. 相似文献