ALKB-8 is a 2-oxoglutarate-dependent di-oxygenase homologous to bacterial AlkB, which oxidatively demethylates DNA substrates. The mammalian AlkB family contains AlkB homologues denominated ALKBH1 to 8 and FTO. The C. elegans genome
includes five AlkB-related genes, homologues of ALKBH1, 4, 6, 7, and 8, but lacks homologues of ALKBH2, 3, and 5 and FTO. ALKBH8 orthologues differ from other AlkB family members by possessing an additional methyltransferase module and an RNA binding N-terminal module. The ALKBH8 methyltransferase domain generates the wobble nucleoside 5-methoxycarbonylmethyluridine from its precursor 5-carboxymethyluridine and its (R)- and (S)-5-methoxycarbonylhydroxymethyluridine hydroxylated forms in tRNAArgUCG and tRNAGlyUCC. The ALKBH8/ALKB-8 methyltransferase domain is highly similar to yeast TRM9, which selectively modulates translation of mRNAs enriched with AGA and GAA codons under both normal and stress conditions. In this report, we studied the role of alkb-8 in C. elegans. We show that downregulation of alkb-8increases detection of lysosome-related organelles visualized by Nile red in vivo. Reversely, forced
expression of alkb-8 strongly decreases the detection of this compartment. In addition, overexpression of alkb-8 applied in a pulse during the L1 larval stage increases the C. elegans lifespan. and Corresponding author: Marta Kostrouchová
Karcinom prsu je nejčastější nádorové onemocnění u žen. Každoročně postihuje více než 1 000 000 žen na celém světě. Z toho zhruba 11 % případů rakoviny prsu lze připisovat konzumaci alkoholu u žen. Cílem tohoto článku je vytvořit představu o podílu nákladů na léčbu karcinomu prsu, který lze přiřadit konzumaci alkoholu v ČR v roce 2007. Zjištěná výsledná částka, kterou je třeba vynaložit na léčbu pacientek pravidelně konzumujících alkohol, je 39 mil. Kč., Breast cancer is the most common cancer in women. Annually, it affects more than 1 million women worldwide. Thereof, some 11% of the breast cancer incidence can be attributed to alcohol consumption in women. The aim of this article is to create a notion of the proportion of the costs spent to treat breast cancer that can be ascribed to alcohol consumption in the Czech Republic in 2007. The overall amount that is to be spent to treat women patients who regularly consume alcohol is 39 million CZK., Iva Šmídová, and Literatura 20
The optimization of functions subject to partial differential equations (PDE) plays an important role in many areas of science and industry. In this paper we introduce the basic concepts of PDE-constrained optimization and show how the all-at-once approach will lead to linear systems in saddle point form. We will discuss implementation details and different boundary conditions. We then show how these system can be solved efficiently and discuss methods and preconditioners also in the case when bound constraints for the control are introduced. Numerical results will illustrate the competitiveness of our techniques.
More than 60 neuropeptides that inhibit juvenile hormone synthesis by the corpora allata have been isolated from the brains of various insect species. Most of them are characterized by a common C-terminal pentapeptide sequence Y/FXFGL/I/V (allatostatin A family, allatostatin superfamily). Besides the allatostatin A family, allatostatic neuropeptides belonging to other two peptide families (W2W9)-allatostatins or allatostatin B family; lepidopteran allatostatin) were reported. So far, only one allatotropin has been identified. Here we discuss latest literature on the multiplicity and multifunctionality of the allatoregulating neuropeptides, their physiological significance as well as their evolutionary conservation in structure and function., Klaus H. Hoffmann, Martina Meyering-Vos, Matthias W. Lorenz, and Lit
Four peptides with allatostatic activity were isolated from brains of the Mediterranean field cricket, Gryllus bimaculatus. Three of them (Grb-AST A3: AGMYSFGL-NH2; Grb-AST A4: SRPFGFGL-NH2; Grb-AST A5: GPDHRFAFGL-NH2) belong to the wide-spread family of Y/FXFGL/I-amide peptides, the fourth (Grb-AST B5: AWDQLRPGW-NH2) is a member of the W2W9 - amide family of neuropeptides. All of these peptides are potent inhibitors of juvenile hormone (JH) biosynthesis by cricket corpora allata in vitro, causing 50% inhibition of JH biosynthesis at 0.4-3 × 10-8 M. The two peptides Grb-AST A5 and Grb-AST B5 have virtually the same potency and efficacy in inhibiting JH biosynthesis in vitro. No synergistic effect of the two peptide families with respect to the inhibition of JH biosynthesis could be observed. Peptides of both families decrease the accumulation of methylfarnesoate, the direct precursor of JH, within CA that have been incubated in farnesol-rich medium. This suggests an involvement of these ASTs in the late steps of JH biosynthesis., Mathias W., Roland Kellner, Klaus H. Hoffmann, and Lit
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.