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It was shown that after UV-irradiation of Ehrlich ascites tumor cells with doses suppressing DNA replication, DNA-protein cross-links were mainly predominantly in the nuclear matrix as compared to peripheral chromatin. A modified method of determining DNA-protein cross-links in the nuclear matrix preparations is proposed. 相似文献
3.
Maurer-Stroh S Koranda M Benetka W Schneider G Sirota FL Eisenhaber F 《PLoS computational biology》2007,3(4):e66
Three different prenyltransferases attach isoprenyl anchors to C-terminal motifs in substrate proteins. These lipid anchors serve for membrane attachment or protein-protein interactions in many pathways. Although well-tolerated selective prenyltransferase inhibitors are clinically available, their mode of action remains unclear since the known substrate sets of the various prenyltransferases are incomplete. The Prenylation Prediction Suite (PrePS) has been applied for large-scale predictions of prenylated proteins. To prioritize targets for experimental verification, we rank the predictions by their functional importance estimated by evolutionary conservation of the prenylation motifs within protein families. The ranked lists of predictions are accessible as PRENbase (http://mendel.imp.univie.ac.at/sat/PrePS/PRENbase) and can be queried for verification status, type of modifying enzymes (anchor type), and taxonomic distribution. Our results highlight a large group of plant metal-binding chaperones as well as several newly predicted proteins involved in ubiquitin-mediated protein degradation, enriching the known functional repertoire of prenylated proteins. Furthermore, we identify two possibly prenylated proteins in Mimivirus. The section HumanPRENbase provides complete lists of predicted prenylated human proteins-for example, the list of farnesyltransferase targets that cannot become substrates of geranylgeranyltransferase 1 and, therefore, are especially affected by farnesyltransferase inhibitors (FTIs) used in cancer and anti-parasite therapy. We report direct experimental evidence verifying the prediction of the human proteins Prickle1, Prickle2, the BRO1 domain-containing FLJ32421 (termed BROFTI), and Rab28 (short isoform) as exclusive farnesyltransferase targets. We introduce PRENbase, a database of large-scale predictions of protein prenylation substrates ranked by evolutionary conservation of the motif. Experimental evidence is presented for the selective farnesylation of targets with an evolutionary conserved modification site. 相似文献
4.
The intracellular linker L(III-IV) of voltage-gated sodium channels is known to be involved in their mechanism of inactivation. Its primary sequence is well conserved in sodium channels from different tissues and species. However, the role of charged residues in this region, first thought to play an important role in inactivation, has not been well identified, whereas the IFM triad (I1488-M1490) has been characterized as the crucial element for inactivation. In this work, we constructed theoretical models and performed molecular dynamics simulations, exploring the role of L(III-IV)-charged residues in the presence of a polar/nonpolar planar interface represented by a dielectric discontinuity. From structural predictions, two alpha-helical segments are proposed. Moreover, from dynamics simulations, a time-conserved motif is detected and shown to play a relevant role in guiding the inactivation particle toward its receptor site. 相似文献
5.
A convenient model for studying the mechanisms of biological self-organization is described by morphometric investigation of formation of mitochondrion associations in medium containing physiological concentration of potassium ions without nonpolar substances. Association formation was considerably better at 15-18 degrees C during isolation and storage than at 0 degree C. The existence of filamented mitochondria in homogenate was also shown by staining of succinate dehydrogenase. Formation of associations increased in medium pretreated with negative air ions carrying superoxide and is probably due to hydrogen peroxide. The effect of substances influencing the surface charge on association formation was studied. 相似文献
6.
Cognitive processes and functional state of mitochondria in brain structures of Wistar rats were studied after intrahippocampal injection of kainic acid, an agonist of glutamate receptors. A single administration of 0.25 μg kainic acid into the dorsal part of the left and right hippocampi affected task retrieval and decreased inhibition of unrewarded responses. The injection of 0.75 μg kainic acid induced recurrent seizures and completely disorganized animal behavior. The functional state of mitochondria, as an important marker of excitotoxicity, was studied after intrahippocampal injections of kainic acid in the same doses. Kainic acid at 0.25 μg proved to activate the oxidative phosphorylation in hippocampal mitochondria. A higher (epileptogenic) dose of kainic acid inhibited mitochondrial respiration in the frontal cortex, but had an insignificant effect on mitochondrial respiration in the hippocampus. The disturbed interaction between the hippocampal system and frontal cortex after kainic acid administration can be the main factor of the revealed cognitive dysfunctions. 相似文献
7.
Malakhova L Bezlepkin VG Antipova V Ushakova T Fomenko L Sirota N Gaziev AI 《Cellular & molecular biology letters》2005,10(4):721-732
Changes in the number of mitochondrial DNA (mtDNA) copies in the brain and spleen tissues of gamma-irradiated (3 Gy) mice were studied by comparative analysis of the long-extension PCR products of mtDNA (15.9 kb) and a fragment of the cluster nuclear beta-globin gene (8.7 kb) amplified simultaneously in one and the same test-tube within total DNA. The analysis showed that, compared to the nuclear beta-globin gene, an increase in mtDNA copy number (polyploidization) took place in the brain and spleen cells of mice exposed to gamma-radiation. This data led to the suggestion that the major mechanism for maintenance of the mitochondrial genome, which is constantly damaged by endogenous ROS and easily affected by ionizing radiation or other exogenous factors, is the induction of synthesis of new mtDNA copies on intact or little affected mtDNA templates because the repair systems in the mitochondria function at a low level of efficiency. 相似文献
8.
Lack of direct DNA damage in human blood leukocytes and lymphocytes after in vitro exposure to high power microwave pulses 总被引:3,自引:0,他引:3
Chemeris NK Gapeyev AB Sirota NP Gudkova OY Tankanag AV Konovalov IV Buzoverya ME Suvorov VG Logunov VA 《Bioelectromagnetics》2006,27(3):197-203
Currently, the potential genotoxicity of high power microwave pulses (HPMP) is not clear. Using the alkaline single cell gel electrophoresis assay, also known as the alkaline comet assay, we studied the effects of HPMP (8.8 GHz, 180 ns pulse width, peak power 65 kW, pulse repetition frequency 50 Hz) on DNA of human whole-blood leukocytes and isolated lymphocytes. The cell suspensions were exposed to HPMP for 40 min in a rectangular waveguide. The average SAR calculated from the temperature kinetics was about 1.6 kW/kg (peak SAR was about 300 MW/kg). The steady-state temperature rise in the 50 microl samples exposed to HPMP was 3.5 +/- 0.1 degrees C. In independent experiments, we did not find any statistically significant DNA damage manifested immediately after in vitro HPMP exposure of human blood leukocytes or lymphocytes or after HPMP exposure of leukocytes subsequently incubated at 37 degrees C for 30 min. Our results indicate that HPMP under the given exposure conditions did not induce DNA strand breaks, alkali-labile sites, and incomplete excision repair sites, which could be detected by the alkaline comet assay. 相似文献
9.
Men and women differ in susceptibility to many diseases and in responses to treatment. Recent advances in genome-wide association
studies (GWAS) provide a wealth of data for associating genetic profiles with disease risk; however, in general, these data
have not been systematically probed for sex differences in gene-disease associations. Incorporating sex into the analysis
of GWAS results can elucidate new relationships between single nucleotide polymorphisms (SNPs) and human disease. In this
study, we performed a sex-differentiated analysis on significant SNPs from GWAS data of the seven common diseases studied
by the Wellcome Trust Case Control Consortium. We employed and compared three methods: logistic regression, Woolf’s test of
heterogeneity, and a novel statistical metric that we developed called permutation method to assess sex effects (PMASE). After
correction for false discovery, PMASE finds SNPs that are significantly associated with disease in only one sex. These sexually
dimorphic SNP-disease associations occur in Coronary Artery Disease and Crohn’s Disease. GWAS analyses that fail to consider
sex-specific effects may miss discovering sexual dimorphism in SNP-disease associations that give new insights into differences
in disease mechanism between men and women. 相似文献
10.
Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base-driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis. 相似文献