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61.
Eli?ka Pot??ková Kate?ina Hru?ková Jan Bure? Petra Kova?íková Iva A. ?pirková Kate?ina Pravdíková Lucie Kolbabová Tereza Hergeselová Pavlína Ha?ková Hana Jansová Miloslav Machá?ek Anna Jirkovská Vera Richardson Darius J. R. Lane Danuta S. Kalinowski Des R. Richardson Kate?ina Vávrová Tomá? ?im?nek 《PloS one》2014,9(11)
Salicylaldehyde isonicotinoyl hydrazone (SIH) is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability). Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O), which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects. 相似文献
62.
Background and Aims
Genome size is known to affect various plant traits such as stomatal size, seed mass, and flower or shoot phenology. However, these associations are not well understood for species with very large genomes, which are laregly represented by geophytic plants. No detailed associations are known between DNA base composition and genome size or species ecology.Methods
Genome sizes and GC contents were measured in 219 geophytes together with tentative morpho-anatomical and ecological traits.Key Results
Increased genome size was associated with earliness of flowering and tendency to grow in humid conditions, and there was a positive correlation between an increase in stomatal size in species with extremely large genomes. Seed mass of geophytes was closely related to their ecology, but not to genomic parameters. Genomic DNA GC content showed a unimodal relationship with genome size but no relationship with species ecology.Conclusions
Evolution of genome size in geophytes is closely related to their ecology and phenology and is also associated with remarkable changes in DNA base composition. Although geophytism together with producing larger cells appears to be an advantageous strategy for fast development of an organism in seasonal habitats, the drought sensitivity of large stomata may restrict the occurrence of geophytes with very large genomes to regions not subject to water stress. 相似文献63.
In this article, we describe the mutual structural effect of the interaction between the model membranes and polylysine and poly-l-arginine. Vibrational circular dichroism (VCD), a method exceptionally sensitive to the polypeptide structure that has not been established in such studies before, was the primary method of this study. A complementary technique, electronic circular dichroism, was applied to verify the newly obtained results and as a bridge to the previous studies. We used micelles composed of sodium dodecyl sulfate (SDS) as a monolayer membrane model and large unilamellar vesicles composed of phospholipids as a bilayer membrane model. We describe the conformational changes of the polypeptides caused by the interaction with the model membranes. Among others, the presence of the liposomes in the solution generated special conditions for the formation of the α-helical structure of poly-l-arginine; the presence of SDS induced the formation of the β-structure of polylysine. From a methodological point of view, we emphasize the advantages of infrared spectroscopic techniques for the liposomic membrane studies as well as the preference of ultraviolet techniques for smaller micellar systems. 相似文献
64.
Kozísek M Sasková KG Rezácová P Brynda J van Maarseveen NM De Jong D Boucher CA Kagan RM Nijhuis M Konvalinka J 《Journal of virology》2008,82(12):5869-5878
65.
Michal Hejcman Irena Žáková Miloslav Bílek Pavla Bendová Pavla Hejcmanová Vilém Pavlů Martina Stránská 《Biologia》2008,63(4):506-514
The effect of rotational grazing on the sward structure of long-term abandoned grassland and the sheep diet selection were investigated in the Giant Mts (Krkono?e/Karkonosze). The aim of the study was to answer the following questions: (1) Does sheep grazing affect the sward structure of previously abandoned mountain grassland? (2) How does sheep diet selection develop within and among grazing seasons? (3) Which section of a pasture do sheep prefer to graze? Data was collected three times during each grazing season in spring, summer and in autumn in the years 2001, 2002 and 2003 Fifty 1 × 1 m plots were used where the plant species occurrence and damage of plants by grazing for all species were repeatedly recorded. 1) Nonsignificant changes in plant species occurrences were recorded in spite of obvious visual changes in sward structure due to grazing e.g. the retreat of tall dominant species characteristic of long-term unmanaged grasslands. 2) Seasonal as well as inter-annual changes in sheep diet selection were detected. In spring 2001, sheep grazed over a wide variety of plant species in low quantities. In subsequent springs, they preferred species favoured during previous autumns (Veratrum album subsp. lobelianum; Ranunculus platanifolius; Senecio ovatus) and changed the diet only as a result of the elimination of favoured plants. 3) Sheep preferred to graze at the highest elevated part of the pasture probably as a consequence of anti-predator behaviour not due to higher occurrence of favoured plant species or the presence of a drinking place or salt licks. Changes in the sward structure were mostly of a quantitative not qualitative character, thus the presence-absence data collection is not a suitable method for monitoring the effects of management restoration. The diet selection changed probably due to the animals’ experience; sheep had no experience with montane species in spring 2001. The sheep were able to recognize favoured plant species after 6 months of wintering in lowland. 相似文献
66.
Král V Mader P Collard R Fábry M Horejsí M Rezácová P Kozísek M Závada J Sedlácek J Rulísek L Brynda J 《Proteins》2008,71(3):1275-1287
Specific antibodies interfere with the function of human tumor-associated carbonic anhydrase IX (CA IX), and show potential as tools for anticancer interventions. In this work, a correlation between structural elements and thermodynamic parameters of the association of antibody fragment Fab M75 to a peptide corresponding to its epitope in the proteoglycan-like domain of CA IX, is presented. Comparisons of the crystal structures of free Fab M75 and its complex with the epitope peptide reveal major readjustments of CDR-H1 and CDR-H3. In contrast, the overall conformations and positions of CDR-H2 and CDR-L2 remain unaltered, and their positively charged residues may thus present a fixed frame for epitope recognition. Adoption of the altered CDR-H3 conformation in the structure of the complex is accompanied by an apparent local stabilization. Analysis of domain mobility with translation-libration-screw (TLS) method shows that librations of the entire heavy chain variable domain (V(H)) decrease and reorient in the complex, which correlates well with participation of the heavy chain in ligand binding. Isothermal titration microcalorimetry (ITC) experiments revealed a highly unfavorable entropy term, which can be attributed mainly to the decrease in the degrees of freedom of the system, the loss of conformational freedom of peptide and partially to a local stabilization of CDR-H3. Moreover, it was observed that one proton is transferred from the environment to the protein-ligand complex upon binding. Molecular dynamics simulations followed by molecular mechanics/generalized Born surface area (MM-GBSA) calculations of the ligand (epitope peptide) binding energy yielded energy values that were in agreement with the ITC measurements and indicated that the charged residues play crucial role in the epitope binding. Theoretical arguments presented in this work indicate that two adjacent arginine residues (ArgH50 and ArgH52) are responsible for the observed proton transfer. 相似文献
67.
The genes of ribosomal RNA are the most popular and frequently used markers for bacterial phylogeny and reconstruction of insect-symbiont coevolution. In primary symbionts, such as Buchnera and Wigglesworthia, genome economization leads to the establishment of a single copy of these sequences. In phylogenetic studies, they provide sufficient information and yield phylogenetic trees congruent with host evolution. In contrast, other symbiotic lineages (e.g., the genus Arsenophonus) carry a higher number of rRNA copies in their genomes, which may have serious consequences for phylogenetic inference. In this study, we show that in Arsenophonus triatominarum the degree of heterogeneity can affect reconstruction of phylogenetic relationships and mask possible coevolution between the symbiont and its host. Phylogenetic arrangement of individual rRNA copies was used, together with a calculation of their divergence time, to demonstrate that the incongruent 16S rDNA trees and low nucleotide diversity in the secondary symbiont could be reconciled with the coevolutionary scenario. 相似文献
68.
Tomáš Pavlíček Petr Bureš Lucie Horová Olga Raskina Eviatar Nevo 《Central European Journal of Biology》2008,3(1):83-90
Using DAPI flow cytometry, we examined genome size divergence of the Persian violet, Cyclamen persicum (Primulaceae) (2n=48) on close opposite slopes of Evolution Canyon (EC), Mt. Carmel, Israel. The range of genome size variation
detected among measured cyclamens was 6.41% in relation to the smallest measured DNA content. Our data on C. persicum at EC showed that local variability in the 2C-value exists. Significantly less DNA was recorded in plants growing in one
station of the African savannah-like south-facing slope (AS) but not in the remaining two stations of the same slope. We were
not able to reject the null hypothesis that there are no significant interslope differences in the genome size between the
temperate European garrigue-like north-facing slope (ES) and the drier AS. In spite of the nonsignificant interslope trend
for the higher genome size in C. persicum, the data-fusion (meta-analysis) test using correlations between C-values in C. persicum, and earlier studied carob tree (Ceratonia siliqua), trifoil (Lotus peregrinus) and a beetle (Oryzaephilus surinamensis) and their distribution along the aridity gradient indicates a positive relationship between drought and genome size at the
microsite. 相似文献
69.
70.
L Pavlícková D Stys M Soucek J Urban O Hrusková J Sedlácek P Strop 《Archives of biochemistry and biophysics》1992,298(2):753-756
The specificity of the proteinase of myeloblastosis-associated virus (MAV) was studied with (a) 21 substrate-based inhibitors, (b) 9 inhibitors with pseudopalindrome sequences, (c) 8 chimeric inhibitors, and (d) 3 compounds designed as human immunodeficiency virus 1 (HIV-1) proteinase inhibitors. The central inhibitory unit (transition state or cleaved bond analog) and the role of the inhibitor side chains from P4 to P4' were investigated. MAV proteinase prefers an aromatic side chain in P1 and a small aliphatic nonpolar chain in P2 and P2'. Residues in P5 and P4 positions are outside of the short catalytic cleft of the enzyme, but still influence binding considerably. The data obtained provide evidence that the MAV proteinase has generally lower specificity and poorer binding than the HIV proteinase. 相似文献