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21.
Kusakiewicz-Dawid A Bugaj M Dzik JM Gołos B Wińska P Pawełczak K Rzeszotarska B Rode W 《Acta biochimica Polonica》2002,49(1):197-203
2-Deamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) is a potent inhibitor of thymidylate synthase. Its analogue, N(alpha)-[4-[N-[(3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]-N-propargylamino]phenylacetyl]-L-glutamic acid, containing p-aminophenylacetic acid residue substituting p-aminobenzoic acid residue, was synthesized. The new analogue exhibited a moderately potent thymidylate synthase inhibition, of linear mixed type vs. the cofactor, N(5,10)-methylenetetrahydrofolate. The Ki value of 0.34 microM, determined with a purified recombinant rat hepatoma enzyme, was about 30-fold higher than that reported for inhibition of thymidylate synthase from mouse leukemia L1210 cells by ICI 198583 (Hughes et al., 1990, J. Med. Chem. 33, 3060). Growth of mouse leukemia L5178Y cells was inhibited by the analogue (IC50 = 1.26 mM) 180-fold weaker than by ICI 198583 (IC50 = 6.9 microM). 相似文献
22.
Brain size of vertebrates has long been recognized to evolve in close association with basic life‐history traits, including lifespan. According to the cognitive buffer hypothesis, large brains facilitate the construction of behavioral responses against novel socioecological challenges through general cognitive processes, which should reduce mortality and increase lifespan. While the occurrence of brain size–lifespan correlation has been well documented in mammals, much less evidence exists for a robust link between brain size and longevity in birds. The aim of this study was to use phylogenetically controlled comparative approach to test for the relationship between brain size and longevity among 384 avian species from 23 orders. We used maximum lifespan and maximum reproductive lifespan as the measures of longevity and accounted for a set of possible confounding effects, such as allometry, sampling effort, geographic patterns, and life‐history components (clutch size, incubation length, and mode of development). We found that both measures of longevity positively correlated with relative (residual) brain size. We also showed that major diversification of brain size preceded diversification of longevity in avian evolution. In contrast to previous findings, the effect of brain size on longevity was consistent across lineages with different development patterns, although the relatively low strength of this correlation could likely be attributed to the ubiquity of allomaternal care associated with the altricial mode of development. Our study indicates that the positive relationship between brain size and longevity in birds may be more general than previously thought. 相似文献
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Piotr Indykiewicz Patrycja Podlaszczuk Aleksandra Janiszewska Piotr Minias 《Journal of avian biology》2018,49(6)
Urban colonization by wildlife involves a combination of several different mechanisms, including phenotype or genotype sorting, phenotypic plasticity and microevolutionary adaptation. Combination of these processes can produce a rapid phenotypic, but also genetic divergence of urban versus rural populations. Here, we examined the pattern of genetic differentiation between urban and rural populations of a colonial migratory bird, the black‐headed gull Chroicocephalus ridibundus. To this end, we sampled ca 170 individuals from six (two urban and four rural) colonies in northern Poland, and genotyped them at ten microsatellite loci. Our analysis provided evidence for negligible genetic divergence of urban and rural colonies, as assessed with fixation index FST and Nei's unbiased genetic distance D (mean pairwise urban‐rural comparisons: FST = 0.003 ± 0.001 [SE] and D = 0.012 ± 0.006 [SE]). Bayesian clustering methods provided support for homogeneous genetic structure across all urban and rural populations. Also, we found no support for reduced allelic diversity in urban versus rural colonies. These results stand in a stark contrast to the previous findings on the genetic consequences of urbanization in birds. We hypothesize that this pattern could possibly be attributed to the important life‐history characters of the black‐headed gull, including coloniality, migratoriness, and high dispersal propensity. Our study provides a novel insight into the urban landscape genetics, underlining large variation in the mechanisms of urban colonization and its genetic consequences in wild animal populations. 相似文献
24.
Patrycja Konieczna Elisa Schiavi Mario Ziegler David Groeger Selena Healy Ray Grant Liam O’Mahony 《PloS one》2015,10(3)
The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses. 相似文献
25.
Jessica Rodgers Beatriz BanoOtalora Mino D C Belle Sarika Paul Rebecca Hughes Phillip Wright Richard McDowell Nina Milosavljevic Patrycja OrlowskaFeuer Franck P Martial Jonathan Wynne Edward R Ballister Riccardo Storchi Annette E Allen Timothy Brown Robert J Lucas 《EMBO reports》2021,22(5)
There is no consensus on the best inhibitory optogenetic tool. Since Gi/o signalling is a native mechanism of neuronal inhibition, we asked whether Lamprey Parapinopsin (“Lamplight”), a Gi/o‐coupled bistable animal opsin, could be used for optogenetic silencing. We show that short (405 nm) and long (525 nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, respectively, and that combining these wavelengths can be used to achieve intermediate levels of activity. These properties can be applied to produce switchable neuronal hyperpolarisation and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. Expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, with 405 and 525 nm stimuli producing responses of opposite sign in the output neurons of the retina. We conclude that bistable animal opsins can co‐opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and reversible. 相似文献
26.
Cypryk K Kamińska P Kosiński M Pertyńska-Marczewska M Lewiński A 《Endokrynologia Polska》2007,58(4):314-319
INTRODUCTION: Nutrition therapy is an integral part of the management of gestational diabetes mellitus (GDM). Most women with GDM are treated by nutritional management alone. The goal of our study was to compare low and high carbohydrate diets in their effectiveness, safety and tolerability in women with GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a low and those on a high carbohydrate diet (45% vs. 65% respectively of energy supply coming from carbohydrates). The presence of urine ketones was controlled every day. After two weeks daily glucose profiles and compliance with the recommended diets were analysed. RESULTS: Glucose concentration before implementation of the diet regimen did not differ between groups. No changes in fasting blood glucose were noticed in the group that had followed a low carbohydrate diet, although a significant decrease in glucose concentration was observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs. 99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the high carbohydrate diet group fasting and after-breakfast glucose concentration did not change. A significant decrease in glycaemia was noticed after lunch (106 +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05). Ketonuria was not observed in either group. Obstetrical outcomes did not differ between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective and safe. A diet with carbohydrate limitation should be recommended to women who experience the highest glycaemia levels after breakfast. 相似文献
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28.
Sura P Bronowicka-Adamska P Furtak E Wróbel M 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2011,154(3):180-186
The effect of mercury ions on the level of cysteine, glutathione, sulfane sulfur, and on the activity of rhodanese, 3-mercaptopyruvate sulfurtransferase (MPST) and γ-cystathionase in brain, heart muscle, liver, kidneys, testes and skeletal muscle of adult Xenopus laevis was investigated. Frogs of both sexes were exposed for 7 or 14 days to 1.353mgL(-1) (ppm) of mercury chloride (HgCl(2)) dissolved in water. The activity of the investigated enzymes participating in cysteine metabolism depends on cysteine in their active sites. Mercury ions can bind to -SH groups and, therefore, lower the activity of enzymes and change the level of sulfane sulfur, a product of l-cysteine desulfuration. The effect of mercury was found to depend on the time of exposure and the kind of tissue. In the liver, the main site of glutathione biosynthesis, the ratio of GSH to GSSG was essentially unchanged. The total glutathione level was decreased after 7 days of exposure to mercury, similarly as the activity of rhodanese. Sulfane sulfur levels were significantly increased after a shorter duration, while they decreased after a longer time of exposure. The kidney, brain and testes were able to enhance the level of GSH, probably thanks to high γ-glutamyltranspeptidase activity. These tissues showed an increased value of GSH/GSSG ratio during the shorter exposure to mercury. The activity of sulfurtransferases was decreased, especially after the longer exposure to mercury. In the heart and skeletal muscle, the level of GSH, sulfane sulfur, and the activity of the investigated sulfurtransferases was diminished after 14 days of exposure to Hg. It can be concluded that the main mechanism of toxic Hg activity is generation of reactive oxygen species in cells due to depleted GSH level, and a decreased sulfurtransferases activity either by blocking or oxidation of their -SH groups, what in consequence results in a diminished sulfane sulfur levels in tissues, especially the heart and testes. 相似文献
29.
Endothelial cells in tumor vessels display unusual characteristics in terms of survival and angiogenic properties which result from the increased expression of VEGF-D and its autocrine effect. To evaluate mechanisms by which VEGF-D leads to such abnormal phenotype, we searched for proteins with modified expression in HUVECs enriched in the recombinant mature VEGF-D (VEGFDΔNΔC) delivered by adenovirus. Expression of membrane proteins in endothelial cells was characterized by FACS using anti-human IT-Box-135 antibodies. HUVECs transduced with Ad-VEGF-DΔNΔC revealed markedly increased expression of proteins involved in adhesion and migration such as (a) integrins (αVβ5, α2β1, α5β1, αMβ2, αLβ2), (b) matrix metalloproteinases (MMP-2, MMP-9, and MMP-14), (c) components of fibrinolytic system (PAI-1, u-PAR), and (d) CD45, CD98, CD147. Interestingly, there also were numerous proteins with significantly reduced expression, particularly among surface exposed membrane proteins. Thus, it can be concluded that to induce proangiogenic phenotype and facilitate migration of HUVECs, VEGF-DΔNΔC not only upregulates expression of proteins known to participate in the cell-matrix interactions but also silences some membrane proteins which could interfere with this process. 相似文献
30.
Aneta Żabka Justyna Teresa Polit Konrad Winnicki Patrycja Paciorek Jolanta Juszczak Mateusz Nowak Janusz Maszewski 《Plant cell reports》2016,35(8):1655-1669