The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors., E. Biroš, I. Kalina, A. Kohút, E. Bogyiová, J. Šalagovič, I. Šulla., and Obsahuje bibliografii
Cytochrome P450s (P450s) involved in insecticide resistance reduce the efficacy of insecticide-based vector control by rendering vector control ineffective. They are recorded in many species of vectors and have various constitutive and insecticide induction profiles. In this study, the isolation and prediction of the structure of a P450 from a strain of Aedes aegypti originating from Malaysia is reported. Quantitative mRNA expression of this gene and a previously reported P450, CYP4H28v2, in the developmental stages of the mosquito after exposure to sub-lethal concentrations of insecticides is also reported. The isolated P450, CYP4H31v2, is an allelic variant of CYP4H31 and contains several conserved motifs of P450s. The secondary structure of the protein is mostly made up of alpha helices and random coils. The tertiary structure was generated using homology modeling and was of good quality based on structure validation using protein structure assessment tools. CYP4H28v2 and CYP4H31v2 were differentially expressed in the developmental stages of the vector, with a significantly increased expression in adult males. The genes were significantly over-expressed in larvae exposed to deltamethrin and permethrin for 6 h. In the DDT-treated larvae, only CYP4H31v2 was significantly over-expressed after a 6 h exposure. Under-expression of the genes was predominant in larvae treated with the organophosphates malathion and temephos. Though the functions of these P450s are unknown, their response to induction by exposure to insecticides indicates the likely involvement of these genes in insecticide tolerance. and Fatma M. A. El-Garj, Mustafa F.F. Wajidi, Silas W. Avicor.
Epidemiological and clinical studies suggest that asthma is associated with adverse cardiovascular outcomes, but its mechanism is uncertain. 5-Hydroxytryptamine (5-HT) is a mediator involved in asthma and in cardiovascular functioning. Thus, in the present study, we explored whether allergic sensitization in guinea pigs modifies 5-HT-induced contractile responses and 5-HT2A receptor expression in thoracic aorta rings. We found that sensitization produced a significant increase of 100 µM 5-HT-induced contractions of aorta rings (~27 % greater contraction than in non-sensitized animals, p<0.05). Preincubation with 10 nM ketanserin (a 5-HT2A receptor antagonist) reduced by ~30 % (p=0.003) and ~36 % (p=0.005) the area under the curve of 5-HT-induced contractions in aortas from non-sensitized and sensitized animals, respectively. There were no differences between sensitized and non-sensitized animals with respect to mRNA (qPCR) and protein (Western blot) expression of 5-HT2A receptor in thoracic aortas. We concluded that in this guinea pig model of asthma, allergic sensitization is not confined to airways, but also affects arterial contractile responses to 5-HT; changes in the expression of the 5-HT2A receptor appear not to be involved in this phenomenon.
Fundamentals of the theory of system alliances are briefly reviewed. An accent is put on interfaces (IFs). The model of IFs consisting of a pair of finite deterministic automata sharing a part of their internal state space is introduced. The presented model of alliance interface can be successfully implemented for the study of typical phenomena in complex heterogeneous objects with a significant degree of uncertainty.
The spatial distribution of cytotypes can provide valuable insights into the evolution of polyploid complexes. Previously, only tetraploid Allium oleraceum was reported from Slovakia. Analysing 863 individuals from 93 populations from Slovakia revealed an extensive variation in the DNA ploidy levels of Allium oleraceum (3x, 4x, 5x and 6x). Of the main cytotypes, the penta- and tetraploids had strongly overlapping distributions, although the pentaploids exhibited a tendency to occur more frequently in the southern and the tetraploids had a tendency to occur in the northern regions of Slovakia. A triploid cytotype was found in one population in the southern part of Slovakia, which is the third locality worldwide for this cytotype. The hexaploid cytotype was rare and sparsely occurred in western and southern Slovakia. Sixteen per cent of the populations sampled consisted of more than one ploidy level; the most common was a combination of penta- and tetraploids. The cytotypes differed with respect to altitude; the tetraploids were found significantly more frequently at higher altitudes than the penta- and hexaploids. When compared with reanalysed altitudinal distribution data from the Czech Republic divided into two geographic areas (Carpathian and Herzynian) the pattern found in the Carpathian part of the Czech Republic was similar to that in Slovakia, with tetraploids at the higher altitudes. The distribution in the Herzynian part (Bohemian Massif) was just the opposite: the tetraploids were more often found at lower altitudes than the penta- and hexaploids. Both tetra- and pentaploid cytotypes occurred in a wide and similar spectrum of habitats, while hexaploids were limited to human-influenced habitats. A local-scale distribution of cytotypes analysed in detail in the Slovak Karst area, showed surprising differences in the distribution of cytotypes on particular karst plains, which can be related to different land uses. Concerning the contrasting altitudinal differentiation of tetraploids in the regions compared, the results suggest that at least two different types of tetraploids occur in Central Europe. The apparent cytotype diversity in the surrounding Slovak Karst area may suggest the existence of a primary contact zone.
The aim of this study was to test the hypothesis that allopurinol ingestion modifies the slow component of • VO2 kinetics and changes plasma oxidative stress markers during severe intensity exercise. Six recreationally active male subjects were randomly assigned to receive a single dose of allopurinol (300 mg) or a placebo in a double-blind, placebo-controlled crossover design, with at least 7 days washout period between the two conditions. Two hours following allopurinol or placebo intake, subjects completed a 6-min bout of cycle exercise with the power output corresponding to 75 % • VO2 max. Blood samples were taken prior to commencing the exercise and then 5 minutes upon completion. Allopurinol intake caused increase in resting xanthine and hypoxanthine plasma concentrations, however it did not affect the slow component of oxygen uptake during exercise. Exercise elevated plasma inosine, hypoxanthine, and xanthine. Moreover, exercise induced a decrease in total antioxidant status, and sulfhydryl groups. However, no interaction treatment x time has been observed. Short term severe intensity exercise induces oxidative stress, but xanthine oxidase inhibition does not modify either the kinetics of oxygen consumption or reactive oxygen species overproduction., R. A. Olek ... [et al.]., and Obsahuje seznam literatury
Neutral trehalase 1 (Nth1) from Saccharomyces cerevisiae
catalyzes disaccharide trehalose hydrolysis and helps yeast to
survive adverse conditions, such as heat shock, starvation or
oxidative stress. 14-3-3 proteins, master regulators of hundreds
of partner proteins, participate in many key cellular processes.
Nth1 is activated by phosphorylation followed by 14-3-3 protein
(Bmh) binding. The activation mechanism is also potentiated by
Ca2+ binding within the EF-hand-like motif. This review
summarizes the current knowledge about trehalases and the
molecular and structural basis of Nth1 activation. The crystal
structure of fully active Nth1 bound to 14-3-3 protein provided
the first high-resolution view of a trehalase from a eukaryotic
organism and showed 14-3-3 proteins as structural modulators
and allosteric effectors of multi-domain binding partners.
Ivermectin acts as a positive allosteric regulator of several ligand gated channels including the glutamate-gated chloride channel (GluCl), γ-aminobutyric acid type-A receptor, glycine receptor, neuronal α 7-nicotinic receptor and purinergic P2X4 receptor. In most of the ivermect in-sensitive channe ls, the effects of ivermectin include the potentiation of agonist-induced currents at low concentrations and channel opening at higher concentrations. Based on mutagenesis, electrophysiological recordings and functional an alysis of chimeras between ivermectin-sensitive and ivermectin-insensitive receptors, it has been concluded that ivermectin acts by insertion between transmembrane helices. The three-dimensional structure of C. elegans GluCl complexed with ivermectin has revealed the details of the ivermectin-binding site, however, no generic motif of amino acids could accurately predict ivermectin binding site for other ligand gated channels. Here, we will review what is currently known about ivermectin binding and modulation of Cys-loop receptor family of ligand-gated ion channels and what are the critical structur al determinants underlying potentiation of the P2X4 receptor channel., H. Zemkova ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy