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31.
Holger Winter Yosuke Maeda Hiroaki Mitsuya Jiri Zemlicka 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1341-1345
Abstract Lipophilic phosphodiester L-alaninates of acyclic unsaturated nucleoside analogues 1d, 1e, 2d, 2e, 3d, 3e, 4d and 5d were prepared and their antiretroviral activity was examined in ATH8 cell culture infected with HIV-1. A possible mechanism of action of these analogues is discussed. 相似文献
32.
We studied population sizes and mobility of Erebia epiphron and Erebia sudetica, two high mountain butterflies forming endemic subspecies in the Hrubý Jeseník Mountains, Czech Republic. E. epiphron formed two continuous populations containing 100,000 and 4,500 individuals on alpine grasslands. The butterflies moved freely within their habitats, but movements between the two populations were highly unlikely. E. sudetica formed a system of colonies at timberline sites on valley headwalls and in forest clearings. Two such colonies studied in detail contained 4,500 and 450 adults and were interconnected by limited dispersal. The negative exponential function and the sigmoid function (this assumes flat decrease of movements over short distances) were superior to the inverse power function in fitting mobility data for both species. For E. sudetica, the functions describing movements within a habitat differed significantly from total movements, suggesting different behaviours of dispersing individuals. The habitats of E. epiphron are uniform and highly isolated, favouring free within-habitat mobility but prohibiting leaving their boundaries. The habitats of E. sudetica are diverse and disturbance-dependent; leaving such habitats is less risky, and a source-sink model may explain the persistence of the species in the mountains. 相似文献
33.
The European catfish Silurus glanis is an important fish species in both commercial and recreational fisheries. Catfish is a spreading species that was reported to potentially benefit from increasing temperatures. The goal of this study was to estimate long‐term changes in harvest rates of catfish in Central Europe. This study used individual mandatory angling logbooks collected by the Czech Fishing Union in the Czech Republic (Central Europe) over the course of years 1986–2017 (32 years) to assess harvest rates of catfish. This study discovered that harvest of catfish has been increasing over time. Moreover, rivers that previously showed zero harvested catfish are beginning to display higher harvest rates of catfish. Increasing average air temperature and angling effort in the study area have positively affected harvest rates of catfish. The increased harvest of catfish could not be reliably explained by intensive fish stocking. In conclusion, while other studies show that many fish species are negatively affected by human activities and therefore show decreased harvest rates, catfish angling seems to benefit from anthropogenic changes. 相似文献
34.
David Bednar Koen Beerens Eva Sebestova Jaroslav Bendl Sagar Khare Radka Chaloupkova Zbynek Prokop Jan Brezovsky David Baker Jiri Damborsky 《PLoS computational biology》2015,11(11)
There is great interest in increasing proteins’ stability to enhance their utility as biocatalysts, therapeutics, diagnostics and nanomaterials. Directed evolution is a powerful, but experimentally strenuous approach. Computational methods offer attractive alternatives. However, due to the limited reliability of predictions and potentially antagonistic effects of substitutions, only single-point mutations are usually predicted in silico, experimentally verified and then recombined in multiple-point mutants. Thus, substantial screening is still required. Here we present FireProt, a robust computational strategy for predicting highly stable multiple-point mutants that combines energy- and evolution-based approaches with smart filtering to identify additive stabilizing mutations. FireProt’s reliability and applicability was demonstrated by validating its predictions against 656 mutations from the ProTherm database. We demonstrate that thermostability of the model enzymes haloalkane dehalogenase DhaA and γ-hexachlorocyclohexane dehydrochlorinase LinA can be substantially increased (ΔT
m = 24°C and 21°C) by constructing and characterizing only a handful of multiple-point mutants. FireProt can be applied to any protein for which a tertiary structure and homologous sequences are available, and will facilitate the rapid development of robust proteins for biomedical and biotechnological applications. 相似文献
35.
Neuzil J 《Biochemical and biophysical research communications》2002,293(5):1309-1313
With the advent of the third millennium, a number of pathologies have been eradicated or taken under control. However, the incidences, of cancer and atherosclerosis, the two most common causes of death in developed countries, have increased or, in some instances, only stagnated. Therefore there has been an intensive search for agents effective against such life-threatening conditions. Accordingly, the potential anti-atherogenic activity of vitamin E analogs has been studied extensively. Interestingly, recent reports strongly suggest that certain vitamin E analogs, represented in particular by alpha-tocopheryl succinate (alpha-TOS), also possess anti-neoplastic activity. In this communication, we review our current understanding of the molecular basis for these double effects of alpha-TOS and propose a testable hypothesis, according to which this semi-synthetic analog exerts both anti-atherogenic and anti-neoplastic activities. We propose that the prevalence of each activity depends on the actual form of the vitamin E analog. That is, the conversion of the pro-vitamin E form, alpha-TOS, to the corresponding vitamin form, alpha-tocopherol, makes this anti-neoplastic agent active against inflammatory diseases like atherosclerosis. 相似文献
36.
Hana Sebestova Miluse Vozdova Svatava Kubickova Halina Cernohorska Radim Kotrba Jiri Rubes 《Chromosoma》2016,125(1):137-149
37.
Zemlicka J 《Biochimica et biophysica acta》2002,1587(2-3):276-286
In order to overcome restrictions imposed by activation (phosphorylation) mechanism of antiviral and antitumor nucleoside analogues several prodrug approaches have been designed. Lipophilic pronucleotides are capable of intracellular delivery of monophosphates of nucleoside analogues, thus circumventing the limitations of enzymic phosphorylation. One of the successful approaches employs lipophilic amino acid ester (alanine) phenyl phosphoramidates as pronucleotides. This approach was applied to AIDS drugs such as AZT, d4T and related analogues but also to nonclassical nucleoside analogues based on allenic and methylenecyclopropane structure. Antiviral effects of the parent analogues were in many cases increased by conversion to phenyl phosphoralaninate (PPA) pronucleotides. Although cytotoxicity increase frequently accompanies antiviral effects of these pronucleotides, a favorable selectivity index can be obtained by manipulation of the parent structure as shown, e.g., for 2,6-diaminopurine methylenecyclopropane pronucleotide 15c. A lack of in vivo toxicity was demonstrated for 2-amino-6-methoxypurine methylenecyclopropane pronucleotide 15e in mice. The PPA pronucleotides can overcome deficiency of phosphorylating enzymes and offer favorable cross-resistance patterns when compared with other antiviral drugs. 相似文献
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40.
Filamentous Alphaproteobacteria associated with bulking in industrial wastewater treatment plants 总被引:1,自引:0,他引:1
Levantesi C Beimfohr C Geurkink B Rossetti S Thelen K Krooneman J Snaidr J van der Waarde J Tandoi V 《Systematic and applied microbiology》2004,27(6):716-727
The phylogeny and distribution of filamentous Alphaproteobacteria, morphologically similar to “Nostocoida limicola” and Eikelboom Type 021N that cause the solids separation problem of bulking in industrial activated sludge plants is described here. A combination of culture-dependent and culture-independent molecular methods has characterized 5 novel species. 16S rRNA targeted oligonucleotide probes were designed for their in situ identification by fluorescence in situ hybridisation (FISH) and used to monitor their presence in 86 WWTPs treating different industrial effluents in four European countries. The involvement of these bacteria in bulking in these plants was confirmed. Filaments hybridising with the ALF-968 probe for the Alphaproteobacteria were present in 65% of the WWTPs examined. They were dominant and therefore probably responsible for bulking in 25.5% of them. The heterogeneous filamentous alphaproteobacterial populations in these communities could be completely identified after application of the oligonucleotide probes used in this study in 91% of the plants containing them. The only filamentous Alphaproteobacteria retrieved in pure culture was isolated from three different industrial WWTPs plants. None of these isolates could grow anaerobically on glucose or denitrify, but all grew aerobically and heterotrophically on a range of carbon sources. Although morphologically similar to the Eikelboom Type 021N morphotype, they were not involved in sulphur metabolism. These bacteria accumulated lipidic storage granules that were associated with their presence under the unbalanced growth conditions existing in these plants. 相似文献