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1.
Zoltán Máté Marietta Zita Poles Gábor Szabó Mária Bagyánszki Petra Talapka Éva Fekete Nikolett Bódi 《Cell and tissue research》2013,352(2):199-206
Cholecystokinin (CCK) is an early marker of both neuronal and endocrine cell lineages in the developing gastrointestinal tract. To determine the quantitative properties and the spatial distribution of the CCK-expressing myenteric neurones in early postnatal life, a transgenic mouse strain with a CCK promoter-driven red fluorescent protein (DsRedT3/CCK) was established. The cell-specific expression of DsRedT3/CCK was validated by in situ hybridization with a CCK antisense riboprobe and by in situ hybridization coupled with immunohistochemistry involving a monoclonal antibody to CCK. A gradual increase in the DsRedT3/CCK-expressing enteric neurones with clear regional differences was documented from birth until the suckling to weaning transition, in parallel with the period of rapid intestinal growth and functional maturation. To evaluate the proportion of myenteric neurones in which DsRedT3/CCK transgene expression was colocalized with the enteric neuronal marker peripherin, immunofluorescence techniques were applied. All DsRedT3/CCK neurones were peripherin-immunoreactive and the proportion of DsRedT3/CCK-expressing myenteric neurones in the duodenum was the highest after the third week of life, when the number of peripherin-immunoreactive myenteric neurones in this region had decreased. Nearly all of the DsRedT3/CCK-expressing neurones also expressed 5-hydroxytryptophan (5-HT). Thus, by utilizing a new transgenic mouse strain, we have demonstrated a small number of CCK-expressing myenteric neurones with a developmentally regulated spatiotemporal distribution. The coexistence of CCK and 5-HT in the majority of these neurones suggests their possible regulatory role in feeding at the suckling to weaning transition. 相似文献
2.
Nikolett Kállai Oliver Luhn Judit Dredán Kristóf Kovács Miléna Lengyel István Antal 《AAPS PharmSciTech》2010,11(1):383-391
The objective of the present study was to investigate the effect of the pellet core materials isomalt, sugar, and microcrystalline cellulose on the in vitro drug release kinetics of coated sustained-release pellets as well as to evaluate the influence of different ratios of polymethacrylate copolymers exhibiting different permeability characteristics on the drug release rate. For characterization of the drug release process of pellets, the effect of osmolality was studied using glucose as an osmotically active agent in the dissolution medium. The pellet cores were layered with diclofenac sodium as model drug and coated with different ratios of Eudragit® RS30D and Eudragit® RL30D (ERS and ERL; 0:1 and 0.5:0.5 and 1:0 ratio) in a fluid bed apparatus. Physical characteristics such as mechanical strength, shape, and size proved that the inert cores were adequate for further processing. The in vitro dissolution tests were performed using a USP Apparatus I (basket method). The results demonstrated that, besides the ratio of the coating polymers (ERS/ERL), the release mechanism was also influenced by the type of starter core used. Sugar- and isomalt-type pellet cores demonstrated similar drug release profiles. 相似文献
3.
Nikolett Mihala Antal Csámpai Janez Ilas Danijel Kikelj Robert Kiss Helga Süli-Vargha 《Journal of peptide science》2006,12(10):663-669
Alternative RGD mimetics-with the exception of glycine-c(Arg-Asp) 1, c(Arg-Glu) 2 and c[Arg-Asp(Phe-OH)] 3 were synthesized. The DKPs were prepared on solid phase with orthogonal protection allowing further derivatization in solution. During solution phase cyclization in NH(3)/methanol, the side chain benzyl ester group of H-Arg(Tos)-Asp(OBzl)-OMe and H-Arg(Tos)-Glu(OBzl)-OMe suffer transesterification, while beta-t-butyl or beta-cyclohexyl esters are stable under the same conditions. In spite of the simple structure, all compounds bind selectively to the alpha(v)beta(3) integrin receptor, 3 showing the highest affinity with an IC(50) value of 0.74 microM value. On the other hand only 3 binds with measurable activity to the alpha(IIb)beta(3) receptor (IC(50) 159 microM). The binding affinities seem to be in accordance with the distances between the arginine guanidino and the aspartic acid carboxyl group in extended conformation determined by semiempirical geometry optimization. 相似文献
4.
Miklós Sárvári Pál Kocsis Levente Deli Dávid Gajári Szabolcs Dávid Zsófia Pozsgay Nikolett Heged?s Károly Tihanyi Zsolt Liposits 《PloS one》2014,9(5)
The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin''s BOLD effect in a region specific manner. In females, the estradiol milieu does not influence the BOLD response to ghrelin. 相似文献
5.
Dvid Keresztes Anita Csizmarik Nikolett Nagy Orsolya Mdos Tams Fazekas Thilo Bracht Barbara Sitek Kathrin Witzke Martin Puhr Sabina Sevcenco Gero Kramer Shahrokh Shariat Zsfia Küronya Lszl Takcs Ilona Tornyi Jzsef Lzr Boris Hadaschik Andrs Lszik Mikls Szcs Pter Nyirdy Tibor Szarvas 《Journal of cellular and molecular medicine》2022,26(4):1332
Baseline or acquired resistance to docetaxel (DOC) represents a significant risk for patients with metastatic prostate cancer (PC). In the last years, novel therapy regimens have been approved providing reasonable alternatives for DOC‐resistant patients making prediction of DOC resistance of great clinical importance. We aimed to identify serum biomarkers, which are able to select patients who will not benefit from DOC treatment. DOC‐resistant PC3‐DR and DU145‐DR sublines and their sensitive parental cell lines (DU145, PC3) were comparatively analyzed using liquid chromatography‐coupled tandem mass spectrometry (LC‐MS/MS). Results were filtered using bioinformatics approaches to identify promising serum biomarkers. Serum levels of five proteins were determined in serum samples of 66 DOC‐treated metastatic castration‐resistant PC patients (mCRPC) using ELISA. Results were correlated with clinicopathological and survival data. CD44 was subjected to further functional cell culture analyses. We found at least 177 two‐fold significantly overexpressed proteins in DOC‐resistant cell lines. Our bioinformatics method suggested 11/177 proteins to be secreted into the serum. We determined serum levels of five (CD44, MET, GSN, IL13RA2 and LNPEP) proteins in serum samples of DOC‐treated patients and found high CD44 serum levels to be independently associated with poor overall survival (p = 0.001). In accordance, silencing of CD44 in DU145‐DR cells resulted in re‐sensitization to DOC. In conclusion, high serum CD44 levels may help identify DOC‐resistant patients and may thereby help optimize clinical decision‐making regarding type and timing of therapy for mCRPC patients. In addition, our in vitro results imply the possible functional involvement of CD44 in DOC resistance. 相似文献
6.
Tékus E Kaj M Szabó E Szénási NL Kerepesi I Figler M Gábriel R Wilhelm M 《Acta biologica Hungarica》2012,63(Z1):89-98
Several studies have described high correlation of salivary and blood lactate level during exercise. Measuring the effectiveness and intensity of training, lactate concentration in blood, and lately in saliva are used.The aim of our study was to evaluate the correlation between the concentration and timing of salivary and blood lactate level in endurance athletes and non-athletes after a maximal treadmill test, and to identify physiological and biochemical factors affecting these lactate levels.Sixteen volunteers (8 athletes and 8 non-athletes) performed maximal intensity (Astrand) treadmill test. Anthropometric characteristics, body composition and physiological parameters (heart rate, RR-variability) were measured in both studied groups. Blood and whole saliva samples were collected before and 1, 4, 8, 12, 15, 20 min after the exercise test. Lactate level changes were monitored in the two groups and two lactate peaks were registered at different timeperiods in athletes. We found significant correlation between several measured parameters (salivary lactate - total body water, salivary lactate - RR-variability, maximal salivary lactate - maximal heart rate during exercise, salivary- and blood lactate -1 min after exercise test). Stronger correlation was noted between salivary lactate and blood lactate in athletes, than in controls. 相似文献
7.
Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction 总被引:7,自引:1,他引:6
Belteki G Haigh J Kabacs N Haigh K Sison K Costantini F Whitsett J Quaggin SE Nagy A 《Nucleic acids research》2005,33(5):e51
Here we describe a triple transgenic mouse system, which combines the tissue specificity of any Cre-transgenic line with the inducibility of the reverse tetracycline transactivator (rtTA)/tetracycline-responsive element (tet-O)-driven transgenes. To ensure reliable rtTA expression in a broad range of cell types, we have targeted the rtTA transgene into the ROSA26 locus. The rtTA expression, however, is conditional to a Cre recombinase-mediated excision of a STOP region from the ROSA26 locus. We demonstrate the utility of this technology through the inducible expression of the vascular endothelial growth factor (VEGF-A) during embryonic development and postnatally in adult mice. Our results of adult induction recapitulate several different hepatic and immune cell pathological phenotypes associated with increased systemic VEGF-A protein levels. This system will be useful for studying genes in which temporal control of expression is necessary for the discovery of the full spectrum of functions. The presented approach abrogates the need to generate tissue-specific rtTA transgenes for tissues where well-characterized Cre lines already exist. 相似文献
8.
Miklos Blaho Tamas Herczeg Gyorgy Kriska Adam Egri Denes Szaz Alexandra Farkas Nikolett Tarjanyi Laszlo Czinke Andras Barta Gabor Horvath 《PloS one》2014,9(7)
The horizontally polarizing surface parts of shiny black cars (the reflection-polarization characteristics of which are similar to those of water surfaces) attract water-leaving polarotactic insects. Thus, shiny black cars are typical sources of polarized light pollution endangering water-leaving insects. A new fashion fad is to make car-bodies matt black or grey. Since rough (matt) surfaces depolarize the reflected light, one of the ways of reducing polarized light pollution is to make matt the concerned surface. Consequently, matt black/grey cars may not induce polarized light pollution, which would be an advantageous feature for environmental protection. To test this idea, we performed field experiments with horizontal shiny and matt black car-body surfaces laid on the ground. Using imaging polarimetry, in multiple-choice field experiments we investigated the attractiveness of these test surfaces to various water-leaving polarotactic insects and obtained the following results: (i) The attractiveness of black car-bodies to polarotactic insects depends in complex manner on the surface roughness (shiny, matt) and species (mayflies, dolichopodids, tabanids). (ii) Non-expectedly, the matt dark grey car finish is much more attractive to mayflies (being endangered and protected in many countries) than matt black finish. (iii) The polarized light pollution of shiny black cars usually cannot be reduced with the use of matt painting. On the basis of these, our two novel findings are that (a) matt car-paints are highly polarization reflecting, and (b) these matt paints are not suitable to repel polarotactic insects. Hence, the recent technology used to make matt the car-bodies cannot eliminate or even can enhance the attractiveness of black/grey cars to water-leaving insects. Thus, changing shiny black car painting to matt one is a disadvantageous fashion fad concerning the reduction of polarized light pollution of black vehicles. 相似文献
9.
Forest management has highly modified the structure of the European forests. Harvesting and post-harvest regeneration leads to a simplified forest structure. Our main objective was to detect the effects of habitat structure and forest age on the ground-dwelling spider diversity and assemblage composition of poplar forests at the Hungarian Great Plain. Our results demonstrate that the rarefaction diversity and the number of forest specialists closely correlated with the structural parameters of the forest floor, however, the age and canopy closure did not influence these parameters. According to redundancy analysis, the composition of spider assemblages was determined solely by habitat structure, with habitat structure having a major effect on the species composition and diversity of spider assemblages. A direct effect of forest age on the spider assemblages was not detected, due to the presence of different habitat types in the surrounding landscape, which may serve as suitable habitats for source-populations of spiders with different habitat requirements. Our results highlight the importance structural complexity of forests for maintaining forest spider diversity and preserving the regional species pool of spiders. 相似文献
10.
Ujfalusi Z Kovács M Nagy NT Barkó S Hild G Lukács A Nyitrai M Bugyi B 《The Journal of biological chemistry》2012,287(38):31894-31904
The conformational elasticity of the actin cytoskeleton is essential for its versatile biological functions. Increasing evidence supports that the interplay between the structural and functional properties of actin filaments is finely regulated by actin-binding proteins; however, the underlying mechanisms and biological consequences are not completely understood. Previous studies showed that the binding of formins to the barbed end induces conformational transitions in actin filaments by making them more flexible through long range allosteric interactions. These conformational changes are accompanied by altered functional properties of the filaments. To get insight into the conformational regulation of formin-nucleated actin structures, in the present work we investigated in detail how binding partners of formin-generated actin structures, myosin and tropomyosin, affect the conformation of the formin-nucleated actin filaments using fluorescence spectroscopic approaches. Time-dependent fluorescence anisotropy and temperature-dependent Förster-type resonance energy transfer measurements revealed that heavy meromyosin, similarly to tropomyosin, restores the formin-induced effects and stabilizes the conformation of actin filaments. The stabilizing effect of heavy meromyosin is cooperative. The kinetic analysis revealed that despite the qualitatively similar effects of heavy meromyosin and tropomyosin on the conformational dynamics of actin filaments the mechanisms of the conformational transition are different for the two proteins. Heavy meromyosin stabilizes the formin-nucleated actin filaments in an apparently single step reaction upon binding, whereas the stabilization by tropomyosin occurs after complex formation. These observations support the idea that actin-binding proteins are key elements of the molecular mechanisms that regulate the conformational and functional diversity of actin filaments in living cells. 相似文献