A graph X, with a group G of automorphisms of X, is said to be (G, s)-transitive, for some s\geq 1, if G is transitive on s-arcs but not on (s + 1)-arcs. Let X be a connected (G, s)-transitive graph of prime valency s\geq 5, and Gv the vertex stabilizer of a vertex v \in V (X). Suppose that Gv is solvable. Weiss (1974) proved that |Gv | p(p−1)^{2}. In this paper, we prove that Gv\cong (\mathbb{Z}_{p}\rtimes \mathbb{Z}_{m})× \mathbb{Z}_{n} for some positive integers m and n such that n | m and m | p − 1., Song-Tao Guo, Hailong Hou, Yong Xu., and Obsahuje seznam literatury
Let (G) and i(G) be the domination number and the independent domination number of G, respectively. Rad and Volkmann posted a conjecture that i(G)/ (G) 6 (G)/2 for any graph G, where (G) is its maximum degree (see N. J.Rad, L.Volkmann (2013)). In this work, we verify the conjecture for bipartite graphs. Several graph classes attaining the extremal bound and graphs containing odd cycles with the ratio larger than (G)/2 are provided as well., Shaohui Wang, Bing Wei., and Seznam literatury
Let a \subseteq \mathbb{C} [x1, ..., xn] be a monomial ideal andJ(a^{c}) the multiplier ideal of a with coefficient c. Then J(a^{c}) is also a monomial ideal of \mathbb{C} [x1, ..., xn], and the equality J(a^{c}) = a implies that 0 < c < n + 1. We mainly discuss the problem when J (a) = a or J({a^{n = 1 - \varepsilon }}) = a for all 0 < ε < 1. It is proved that if J (a) = a then a is principal, and if J({a^{n = 1 - \varepsilon }}) = a holds for all 0 < ε < 1 then a = (x1, ..., xn). One global result is also obtained. Let ã be the ideal sheaf on \mathbb{P}^{n-1} associated with a. Then it is proved that the equality J (ã) = ã implies that ã is principal., Cheng Gong, Zhongming Tang., and Obsahuje seznam literatury
The aim of the present work was to study the effect of 3- mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (CMTI), an efficient aldose reductase inhibitor, on sorbitol accumulation in selected organs of streptozotocin-induced diabetic rats in vivo . In addition, the effect of CMTI on aldose reductase back reaction and on sorbitol dehydrogenase was determined. The model of experimental diabetes in male Wistar rats induced by streptozotocin was used. Experimental diabetes was induced by triple intraperitoneal doses of streptozotocin on three consecutive days. In diabetic rats, significant elevation of sorbitol concentration in the sciatic nerve and eye lenses was recorded. CMTI administered intragastrically (50 mg/kg/day) for five consecutive days significantly inhibited sorbitol accumulation in the sciatic nerve, yet it was without effect in eye lenses of diabetic animals. For aldose reductase back reaction, the substrate affinity of glycerol to aldose reductase was one order lower than that of glyceraldehyde in forward reaction. In addition, the back reaction was much slower, characterized by Vmax value of about 30 times lower than that of the forward reaction. Inhibition of aldose reductase by CMTI was characterized by closely related IC50 values in submicromolar range for both forward and back reactions. No significant inhibition of the second enzyme of the polyol pathway, sorbitol dehydrogenase, by 100 μM CMTI was recorded (I=0.9±2.7 %, n=3). To conclude, the presented results showed the ability of CMTI to affect the polyol pathway in diabetic rats in vivo and represent thus a further step in a complex preclinical evaluation of CMTI as a potential agent for treatment of chronic diabetic complications., M. Soltesova Prnova, J. Ballekova, A. Gajdosikova, A. Gajdosik, M. Stefek., and Obsahuje bibliografii
Here we describe the new trypanosomatid, Phytomonas borealis sp. n., from the midgut of the spiked shieldbugs, Picromerus bidens (Linnaeus), collected in two locations, Novgorod and Pskov Oblasts of Russia. The phylogenetic analyses, based on the 18S rRNA gene, demonstrated that this flagellate is a sister species to the secondary monoxenous Phytomonas nordicus Frolov et Malysheva, 1993, which was concurrently documented in the same host species in Pskov Oblast. Unlike P. nordicus, which can complete its development (including exit to haemolymph and penetration into salivary glands) in Picromerus bidens, the new species did not form any extraintestinal stages in the host. It also did not produce endomastigotes, indispensable for transmission in other Phytomonas spp. These observations, along with the fact that P. bidens overwinters at the egg stage, led us to the conclusion that the examined infections with P. borealis were non-specific. Strikingly, the flagellates from the Novgorod population contained prokaryotic endosymbionts, whereas the parasites from the second locality were endosymbiont-free. This is a first case documenting presence of intracellular symbiotic bacteria in Phytomonas spp. We suggest that this novel endosymbiotic association arose very recently and did not become obligate yet. Further investigation of P. borealis and its intracellular bacteria may shed light on the origin and early evolution of endosymbiosis in trypanosomatids., Anna I. Ganyukova, Alexander O. Frolov, Marina N. Malysheva, Viktoria V. Spodareva, Vyacheslav Yurchenko and Alexei Yu. Kostygov., and Obsahuje bibliografii
Endothelin B (ETB) receptors present in abundance the central nervous system (CNS) have been shown to have significant implications in its development and neurogenesis. We have targeted ETB receptors stimulation using a highly specific agonist, IRL-1620, to treat CNS disorders. In a rat model of cerebral ischemia intravenous administration IRL-1620 significantly reduced infarct volume and improved neurological and motor functions compared to control. This improvement, in part, is due to an increase in neuroregeneration. We also investigated the role of IRL-1620 in animal models of Alzheimer’s disease (AD). IRL-1620 improved learning and memory, reduced oxidative stress and increased VEGF and NGF in Aβ treated rats. IRL-1620 also improved learning and memory in an aged APP/PS1 transgenic mouse model of AD. These promising findings prompted us to initiate human studies. Successful chemistry, manufacturing and control along with mice, rat and dog toxicological studies led to completion of a human Phase I study in healthy volunteers. We found that a dose of 0.6 μg/kg of IRL-1620 can be safely administered, three times every four hours, without any adverse effect. A Phase II clinical study with IRL-1620 has been initiated in patients with cerebral ischemia and mild to moderate AD., A. Gulati, M. G. Hornick, S. Briyal, M. S. Lavhale., and Seznam literatury
Nucleoside diphosphate kinases (NDPK) are key enzymes involved in the intracellular nucleotide maintenance in all living organisms, especially in trypanosomatids which are unable to synthesise purines de novo. Four putative NDPK isoforms were identified in the Trypanosoma cruzi Chagas, 1909 genome but only two of them were characterised so far. In this work, we studied a novel isoform from T. cruzi called TcNDPK3. This enzyme presents an atypical N-terminal extension similar to the DM10 domains. In T. cruzi, DM10 sequences targeted other NDPK isoform (TcNDPK2) to the cytoskeleton, but TcNDPK3 was localised in glycosomes despite lacking a typical peroxisomal targeting signal. In addition, TcNDPK3 was found only in the bloodstream trypomastigotes where glycolytic enzymes are very abundant. However, TcNDPK3 mRNA was also detected at lower levels in amastigotes suggesting regulation at protein and mRNA level. Finally, 33 TcNDPK3 gene orthologs were identified in the available kinetoplastid genomes. The characterisation of new glycosomal enzymes provides novel targets for drug development to use in therapies of trypanosomatid associated diseases., María de los Milagros Cámara, León Bouvier, Chantal Reigada, Fabio A. Digirolamo, Melisa Sayé, Claudio A. Pereira., and Obsahuje bibliografii
Autologous vein grafts used as aortocoronary bypasses are often prone to intimal hyperplasia, which results in stenosis and occlusion of the vein. The aim of this study was to prevent intimal hyperplasia using a newly developed perivascular system with sustained release of sirolimus. This system of controlled drug release consists of a polyester mesh coated with a copolymer of L-lactic acid and ε -caprolactone that releases sirolimus. The mesh is intended for wrapping around the vein graft during surgery. The mesh releasing sirolimus was implanted in periadventitial position onto arteria carotis communis of rabbits, and neointimal hyperplasia was then assessed. We found that implanted sirolimus-releasing meshes reduced intima thickness by 47±10 % compared to a vein graft after 3 weeks. The pure polyester mesh decreased vein intima thickness by 35±9 %. Thus, our periadventitial system for controlled release of sirolimus prevented the develo pment of intimal hyperplasia in autologous vein grafts in vivo in rabbits. A perivascularly applied mesh releasing sirolimus is a promising device for preventing stenosis of autologous vein grafts., I. Skalský ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
We have assessed the phylogenetic status of the Leishmania genome project Friedlin reference strain by MLEE and multiprimer RAPD including a set of 9 stocks representative of the main Leishmania species and of the whole genetic diversity of the Leishmania genus. To our knowledge, the detailed genetic characterization of the Friedlin strain has never been published before. As previously recorded (Tibayrenc et al. 1993), MLEE and RAPD data gave congruent phylogenetic results. The Friedlin reference strain was definitely attributed to Leishmania (Leishmania) major Yakimoff et Schokhor, 1914. Five specific RAPD patterns made it possible to distinguish between the Friedlin strain and the 2 other L. (L.) major stocks included in the study. Various specific MLEE and RAPD characters permitted to distinguish between the Leishmania species included in the study. All these characters are usable to detect accidental laboratory mix-ups involving the Friedlin reference strain. In confirmation with previous studies involving a more limited set of genetic markers, the general genetic diversity of the Leishmania genus proved to be considerable. It must be made clear that only one strain cannot be considered as representative of the whole genetic variability of the genus Leishmania. In the future, it is therefore advisable to complement the results obtained in the framework of the Leishmania genome project with data from other strains that should be selected on a criterion of important genetic differences with the Friedlin strain.
Diabetic nephropathy (DN), the most serious complication of Type 1 diabetes (DM1), has a strong genetic component. Cyclooxygenase-2 (COX-2), an in ducible enzyme by a number of stimuli, has been implicated in pathophysiology of cardiovascular and renal disease, including DN. The allele -765C, of the -765G>C polymorphism (rs20417) in the COX-2 promoter has lower promoter activity compared with the -765G allele and protective effects in cardiovascular disease. This polymorphism was not investigated in patients with DM1 and nephropathy. The study was conducted in 779 Caucasian patients with DM1 and compared to a representative sample of healthy Czech population. The patients demonstr ated lower frequencies of the CC genotype (P=0.005). From th e DM1 cohort, 153 patients met the criteria for low risk of the development of DN (LRDN, duration of DM1>10 years, normoalbuminuria, normotension) and 139 patients had manifest DN. There were no differences in -765G>C polymorphisms between LRDN and DN patients. Moreover, the C/G allele frequenc ies did not also differ between the groups. In conclusion, patients with DM1 display lower freqencies of the protective CC genotype as compared to healthy subjects. However, the study did not reveal associations of -765G>C polymorphism with the risk of DN., J. A. Hubáček ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy