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21.
László Kékesi Anna Sipos Gábor Németh János Pató Nóra Breza Ferenc Baska László Őrfi György Kéri 《Bioorganic & medicinal chemistry letters》2013,23(22):6152-6155
A series of novel pyrido[2,3-b]pyrazines were synthesized as potential antitumor agents for erlotinib-resistant tumors. Known signal inhibitor compounds from our Nested Chemical Library were tested in phenotypic assays on erlotinib-sensitive PC9 and erlotinib-resistant PC9-ER cell lines to find a compound class to be active on erlotinib resistant cell lines. Based on the screening data, novel pyrido[2,3-b]pyrazines were designed and synthesized. The effect of the substituent position of the heteroaromatic moiety in position 7 and the importance of unsubstituted position 2 of the pyridopyrazine core were explored. Compound 7n had an IC50 value of 0.09 μM for the inhibition of PC9 and 0.15 μM for the inhibition of PC9-ER. We found that some lead compounds of these structures overcome erlotinib-resistance which might become promising drug candidates to fight against NSCLC with EGFR T790M mutation. The signaling network(s) involved in the mechanism(s) of action of these novel compounds in overcoming erlotinib resistance remain to be elucidated. 相似文献
22.
Eszter Bognar Zsolt Sarszegi Aliz Szabo Balazs Debreceni Nikoletta Kalman Zsuzsanna Tucsek Balazs Sumegi Ferenc Gallyas Jr 《PloS one》2013,8(6)
Background
Red wine polyphenols can prevent cardiovascular and inflammatory diseases. Resveratrol, the most extensively studied constituent, is unlikely to solely account for these beneficial effects because of its rather low abundance and bioavailability. Malvidin is far the most abundant polyphenol in red wine; however, very limited data are available about its effect on inflammatory processes and kinase signaling pathways.Methods & Findings
The present study was carried out by using RAW 264.7 macrophages stimulated by bacterial lipopolysaccharide in the presence and absence of malvidin. From the cells, activation of nuclear factor-kappaB, mitogen-activated protein kinase, protein kinase B/Akt and poly ADP-ribose polymerase, reactive oxygen species production, mitogen-activated protein kinase phosphatase-1 expression and mitochondrial depolarization were determined. We found that malvidin attenuated lipopolysaccharide-induced nuclear factor-kappaB, poly ADP-ribose polymerase and mitogen-activated protein kinase activation, reactive oxygen species production and mitochondrial depolarization, while upregulated the compensatory processes; mitogen-activated protein kinase phosphatase-1 expression and Akt activation.Conclusions
These effects of malvidin may explain the previous findings and at least partially account for the positive effects of moderate red wine consumption on inflammation-mediated chronic maladies such as obesity, diabetes, hypertension and cardiovascular disease. 相似文献23.
24.
Dénes Dudits Katalin T?r?k András Cseri Kenny Paul Anna V. Nagy Bettina Nagy László Sass Gy?rgyi Ferenc Radomira Vankova Petre Dobrev Imre Vass Ferhan Ayaydin 《Plant physiology》2016,170(3):1504-1523
The biomass productivity of the energy willow Salix viminalis as a short-rotation woody crop depends on organ structure and functions that are under the control of genome size. Colchicine treatment of axillary buds resulted in a set of autotetraploid S. viminalis var. Energo genotypes (polyploid Energo [PP-E]; 2n = 4x = 76) with variation in the green pixel-based shoot surface area. In cases where increased shoot biomass was observed, it was primarily derived from larger leaf size and wider stem diameter. Autotetraploidy slowed primary growth and increased shoot diameter (a parameter of secondary growth). The duplicated genome size enlarged bark and wood layers in twigs sampled in the field. The PP-E plants developed wider leaves with thicker midrib and enlarged palisade parenchyma cells. Autotetraploid leaves contained significantly increased amounts of active gibberellins, cytokinins, salicylic acid, and jasmonate compared with diploid individuals. Greater net photosynthetic CO2 uptake was detected in leaves of PP-E plants with increased chlorophyll and carotenoid contents. Improved photosynthetic functions in tetraploids were also shown by more efficient electron transport rates of photosystems I and II. Autotetraploidization increased the biomass of the root system of PP-E plants relative to diploids. Sections of tetraploid roots showed thickening with enlarged cortex cells. Elevated amounts of indole acetic acid, active cytokinins, active gibberellin, and salicylic acid were detected in the root tips of these plants. The presented variation in traits of tetraploid willow genotypes provides a basis to use autopolyploidization as a chromosome engineering technique to alter the organ development of energy plants in order to improve biomass productivity.Energy security and climate change as global problems urge increased efforts to use plants as renewable energy sources both for power generation and transportation fuel production. Selected wood species, such as willows (Salix spp.), can be cultivated as short-rotation coppice for the rapid accumulation of biomass and reduction of CO2 emission. Coppicing reinvigorates shoot growth, resulting in a special woody plant life cycle that differs from natural tree development, which takes decades. In this cultivation system, small stem cuttings are planted at high densities (15,000–25,000 ha−1). In the soil, these dormant wood cuttings first produce roots and shoots that emerge from reactivated buds. During the first year, the growing shoots mature to woody stems. In the winter, these stems are cut back, and in the following spring, the cut stumps develop multiple shoots. The short-rotation coppice plantations are characterized by a very short, 2- to 3-year rotation, and the most productive varieties can produce up to 15 tons of oven-dried wood per hectare per year (Cunniff and Cerasuolo, 2011). The high-density willow plantations can also be efficiently used for heavy metal or organic phytoremediation, as reviewed by Marmiroli et al. (2011).The biomass productivity of shrub willows is largely dependent on coppicing capability, early vigorous growth, shoot growth rate and final stem height, root system size, photosynthetic efficiency, formation and composition of woody stems, water and nutrient use, as well as abiotic and biotic stress tolerance. Genetic improvement of all these traits can be based on broad natural genetic resources represented by more than 400 species in the genus Salix. More than 200 species have hybrid origins, and ploidy levels vary from diploid up to dodecaploid (Suda and Argus, 1968; Newsholme, 1992). In addition to molecular marker-assisted clone selection, intraspecific and interspecific crosses have been shown to further extend genetic variability in breeding programs for biomass yield (Karp et al., 2011).During natural diversification and artificial crossings of Salix spp., the willow genomes frequently undergo polyploidization, resulting in triploid or tetraploid allopolyploids. In triploid hybrids, both heterosis and ploidy can contribute to the improved biomass yield (Serapiglia et al., 2014). While the alloploid triploids have attracted considerable attention in willow improvement, the potentials of autotetraploid willow genotypes have not been exploited so far. As shown for other short-rotation wood species (poplar [Populus spp.], black locust [Robinia pseudoacacia], Paulownia spp., and birch [Betula spp.]), doubling the chromosome set by colchicine treatment can cause significant changes in organ morphology or growth parameters (Tang et al., 2010; Cai and Kang, 2011; Harbard et al., 2012; Mu et al., 2012; Wang et al., 2013a, 2013b). In several polyploidization protocols, the in vitro cultured tissues are exposed to different doses of colchicine or other inhibitors of mitotic microtubule function, and plantlets are differentiated from polyploid somatic cells (Tang et al., 2010; Cai and Kang, 2011). Alternatively, seeds or apical meristems of germinating seedlings can be treated with a colchicine solution (Harbard et al., 2012). Allotetraploids of poplar were produced by zygotic chromosome doubling that was induced by colchicine and high-temperature treatment (Wang et al., 2013a).Since tetraploid willow plants with 2n = 4x = 76 chromosomes are expected to represent novel genetic variability, especially for organ development and physiological parameters, a polyploidization project was initiated that was based on a highly productive diploid energy willow (S. viminalis var. Energo). Colchicine treatment of reactivated axillary buds of the in vitro-grown energy willow plantlets resulted in autotetraploid shoots and, subsequently, plants. For comparison of diploid and tetraploid variants of willow plants, digital imaging of green organs and roots was used for phenotyping. Among the tetraploid lines, genotypes were identified with improved biomass production, better photosynthetic parameters, and altered organ structure and hormone composition. The new tetraploid willow variants produced can serve as a unique experimental material to uncover key factors in biomass production in this short-rotation energy plant. In the future, these plants can also serve as crossing partners of diploid lines for the production of novel triploid energy willow genotypes. 相似文献
25.
Is Foraging Time Limited During Winter? – A Feeding Experiment with Tree Sparrows Under Different Predation Risk
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Small passerines are faced with a trade‐off when foraging during winter. Increasing energy reserves makes them more vulnerable to predators, while a low level of reserves exposes them to a high risk of starvation. Whether small birds under these circumstances are allowed to reduce their foraging activity under increased predation risk, for example in feeding sites more exposed to predators, remains controversial in former behavioural and ecological researches. In this study, we investigated the foraging activity of free‐living Tree Sparrow Passer montanus flocks feeding on an artificial feeding platform. The predation risk perceived by the sparrows was manipulated by placing the platform either close to or far from a bushy shelter. Foraging activity, assessed as cumulative activity of sparrows per unit time on the platform, did not differ between the low‐risk and the high‐risk conditions and did not significantly change during the day. Feeding efficiency, assessed as pecking rate, was not either reduced under the high‐risk condition. Our results suggest that sparrows were forced to feed almost continuously during the day in order to maintain their preferred level of energy reserves. However, several behavioural changes helped sparrows to adopt a safer foraging policy when feeding far from cover, as we found in another study. Altogether, sparrow flocks feeding far from cover decreased the overall foraging time (the time when any sparrow stayed on the platform) by approximately 20% as compared to the near cover condition. A possible way to maintain the same level of foraging activity despite of the reduction in overall foraging time is discussed. 相似文献
26.
Domenico D'Alelio Bruno Hay Mele Simone Libralato Maurizio Ribera d'Alcal Ferenc Jordn 《Ecology and evolution》2019,9(20):11631-11646
Species are characterized by physiological and behavioral plasticity, which is part of their response to environmental shifts. Nonetheless, the collective response of ecological communities to environmental shifts cannot be predicted from the simple sum of individual species responses, since co‐existing species are deeply entangled in interaction networks, such as food webs. For these reasons, the relation between environmental forcing and the structure of food webs is an open problem in ecology. To this respect, one of the main problems in community ecology is defining the role each species plays in shaping community structure, such as by promoting the subdivision of food webs in modules—that is, aggregates composed of species that more frequently interact—which are reported as community stabilizers. In this study, we investigated the relationship between species roles and network modularity under environmental shifts in a highly resolved food web, that is, a “weighted” ecological network reproducing carbon flows among marine planktonic species. Measuring network properties and estimating weighted modularity, we show that species have distinct roles, which differentially affect modularity and mediate structural modifications, such as modules reconfiguration, induced by environmental shifts. Specifically, short‐term environmental changes impact the abundance of planktonic primary producers; this affects their consumers’ behavior and cascades into the overall rearrangement of trophic links. Food web re‐adjustments are both direct, through the rewiring of trophic‐interaction networks, and indirect, with the reconfiguration of trophic cascades. Through such “systemic behavior,” that is, the way the food web acts as a whole, defined by the interactions among its parts, the planktonic food web undergoes a substantial rewiring while keeping almost the same global flow to upper trophic levels, and energetic hierarchy is maintained despite environmental shifts. This behavior suggests the potentially high resilience of plankton networks, such as food webs, to dramatic environmental changes, such as those provoked by global change. 相似文献
27.
Varga B Barabás O Kovári J Tóth J Hunyadi-Gulyás E Klement E Medzihradszky KF Tölgyesi F Fidy J Vértessy BG 《FEBS letters》2007,581(24):4783-4788
Human dUTPase, essential for DNA integrity, is an important survival factor for cancer cells. We determined the crystal structure of the enzyme:alpha,beta-imino-dUTP:Mg complex and performed equilibrium binding experiments in solution. Ordering of the C-terminus upon the active site induces close juxtaposition of the incoming nucleophile attacker water oxygen and the alpha-phosphorus of the substrate, decreasing their distance below the van der Waals limit. Complex interactions of the C-terminus with both substrate and product were observed via a specifically designed tryptophan sensor, suitable for further detailed kinetic and ligand binding studies. Results explain the key functional role of the C-terminus. 相似文献
28.
29.
Ferenc Ötvös Dmitry S. Gembitsky Richard F. Murphy Sándor Lovas 《International journal of peptide research and therapeutics》2007,13(1-2):329-336
Steric requirements of binding [Nle10]NKA(4–10) to NK-2 receptor were studied by introducing conformationally constrained amino acid analogs into its sequence.
Two series of [Nle10]NKA(4–10) analogs were synthesized to investigate (i) the significance of a putative β-turn in the receptor-ligand interaction by insertion of either (S)- or (R)-Gly8{ANC-2}Leu9 γ-lactams to mimic a β-turn constraint, and (ii) the effect of hindered rotation in the Φ, χ1 and χ2 dihedral angle space of the crucially important Phe6 which was replaced systematically with d-Phe, d- and l-Tyr, as well as with their conformationally constrained analogs, Tic, HOTic and β-MePhe. Competition binding experiments
with [3H]NKA were performed using cloned human NK-2 receptors expressed in CHO cells. The analog possessing only an (R)-Gly8{ANC-2}Leu9 constraint, had the same binding affinity as that of the parent peptide. The rank order of potency of the other analogs showed
a cumulative effect of different structural modifications in decreasing the binding affinity, i.e., when changing the configuration of the lactam ring to S, replacing Phe6 with constrained analogs, Tic or β-MePhe, changing the configuration of the amino acid at position six to d, and introducing a hydroxyl group on the aromatic ring.
Ferenc ?tv?s and Dmitry S. Gembitsky - Made an equal contribution.
Abbreviations used for amino acids and peptides follow the recommendations of the IUPAC-IUB Commission of Biochemical Nomenclature,
Eur. J. Biochem. (1984) 138, 9–37 相似文献
30.
Gene expression dynamics in deer antler: mesenchymal differentiation toward chondrogenesis 总被引:6,自引:0,他引:6
Gyurján I Molnár A Borsy A Stéger V Hackler L Zomborszky Z Papp P Duda E Deák F Lakatos P Puskás LG Orosz L 《Molecular genetics and genomics : MGG》2007,277(3):221-235
Annual re-growth of deer antler represents a unique example of complete organ regeneration. Because antler mesenchymal cells
retain their embryonic capacity to develop into cartilage or bone, studying antler development provides a natural system to
follow gene expression changes during mesenchymal differentiation toward chondrogenic/osteogenic lineage. To identify novel
genes involved either in early events of mesenchymal cell specialization or in robust bone development, we have introduced
a 3 K heterologous microarray set-up (deer cDNA versus mouse template). Fifteen genes were differentially expressed; genes
for housekeeping, regulatory functions (components of different signaling pathways, including FGF, TGFβ, Wnt), and genes encoding
members of the Polycomb group were represented. Expression dynamics for genes are visualized by an expression logo. The expression
profile of the gene C21orf70 of unknown function is described along with the effects when over-expressed; furthermore the nuclear localization of the
cognate protein is shown. In this report, we demonstrate the particular advantage of the velvet antler model in bone research
for: (1) identification of mesenchymal and precartilaginous genes and (2) targeting genes upregulated in robust cartilage
development.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献