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51.
52.
Cubrilo D Djordjevic D Zivkovic V Djuric D Blagojevic D Spasic M Jakovljevic V 《Molecular and cellular biochemistry》2011,355(1-2):273-279
Maximal workload in elite athletes induces increased generation of reactive oxygen/nitrogen species (RONS) and oxidative stress, but the dynamics of RONS production are not fully explored. The aim of our study was to examine the effects of long-term engagement in sports with different energy requirements (aerobic, anaerobic, and aerobic/anaerobic) on oxidative stress parameters during progressive exercise test. Concentrations of lactates, nitric oxide (NO) measured through stabile end product-nitrites (NO2 ?), superoxide anion radical (O2 ??), and thiobarbituric reactive substances (TBARS) as index of lipid peroxidation were determined in rest, after maximal workload, and at 4 and 10th min of recovery in blood plasma of top level competitors in rowing, cycling, and taekwondo. Results showed that sportmen had similar concentrations of lactates and O2 ?? in rest. Nitrite concentrations in rest were the lowest in taekwondo fighters, while rowers had the highest levels among examined groups. The order of magnitude for TBARS level in the rest was bicycling > taekwondo > rowing. During exercise at maximal intensity, the concentration of lactate significantly elevated to similar levels in all tested sportsmen and they were persistently elevated during recovery period of 4 and 10 min. There were no significant changes in O2 ??, nitrite, and TBARS levels neither at the maximum intensity of exercise nor during the recovery period comparing to the rest period in examined individuals. Our results showed that long term different training strategies establish different basal nitrites and lipid peroxidation levels in sportmen. However, progressive exercise does not influence basal nitrite and oxidative stress parameters level neither at maximal load nor during the first 10 min of recovery in sportmen studied. 相似文献
53.
Akritopoulou-Zanze I Wakefield BD Gasiecki A Kalvin D Johnson EF Kovar P Djuric SW 《Bioorganic & medicinal chemistry letters》2011,21(5):1476-1479
We report the synthesis and biological evaluation of 5-substituted indazoles and amino indazoles as kinase inhibitors. The compounds were synthesized in a parallel synthesis fashion from readily available starting materials employing [2+3] cycloaddition reactions and were evaluated against a panel of kinase assays. Potent inhibitors were identified for numerous kinases such as Rock2, Gsk3β, Aurora2 and Jak2. 相似文献
54.
55.
Bone microarchitecture at muscle attachment sites: The relationship between macroscopic scores of entheses and their cortical and trabecular microstructural design
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Ksenija Djukic Petar Milovanovic Michael Hahn Björn Busse Michael Amling Marija Djuric 《American journal of physical anthropology》2015,157(1):81-93
The studies of entheses in bioarchaeology attempted to reconstruct the habitual physical activities of past populations. However, the studies of microarchitecture of the underlying bone are still lacking despite well‐known potential of bone internal microarchitecture to reflect mechanical loading. It is unknown whether different morphological expressions of entheseal changes (ECs) correlate with the microstructural characteristics of the underlining bone. This study analyzed bone microstructural characteristics at the entheses. Our focus was on examining the possible successive nature of the three‐stage scale of entheseal macroscopic changes by comparing EC scores with the microarchitectural features at the attachment sites. The study was based on the hypothesis that mechanical loading influences the microarchitecture of the bone at the attachment site. The bone samples were taken from 24 adult male skeletons from medieval cemeteries in Serbia, with different macroscopic expression score of EC. We evaluated the macroscopic and microscopic appearance of four entheses of the lower limbs (origin of the soleus muscle and the insertions of the adductor magnus, gluteus maximus, and iliopsoas muscles). The specimens were scanned using microcomputed tomography (Scanco µCT 40). Our data showed a lack of consistent correlation between stages of the macroscopic scoring systems with microarchitecture at the entheses, only cortical thickness was significantly different between EC stages. Analyzing relationship between trabecular and cortical bone microstructure we found correlations between cortical and trabecular variables only in Stage C. Results of our study suggest that macroscopic EC might not represent distinct successive phases in bone adaptation to mechanical loading. Am J Phys Anthropol 157:81–93, 2015. © 2014 Wiley Periodicals, Inc. 相似文献
56.
Viktorian Miok Saskia M Wilting Mark A van de Wiel Annelieke Jaspers Paula I van Noort Ruud H Brakenhoff Peter JF Snijders Renske DM Steenbergen Wessel N van Wieringen 《BMC bioinformatics》2014,15(1)
Background
To determine which changes in the host cell genome are crucial for cervical carcinogenesis, a longitudinal in vitro model system of HPV-transformed keratinocytes was profiled in a genome-wide manner. Four cell lines affected with either HPV16 or HPV18 were assayed at 8 sequential time points for gene expression (mRNA) and gene copy number (DNA) using high-resolution microarrays. Available methods for temporal differential expression analysis are not designed for integrative genomic studies.Results
Here, we present a method that allows for the identification of differential gene expression associated with DNA copy number changes over time. The temporal variation in gene expression is described by a generalized linear mixed model employing low-rank thin-plate splines. Model parameters are estimated with an empirical Bayes procedure, which exploits integrated nested Laplace approximation for fast computation. Iteratively, posteriors of hyperparameters and model parameters are estimated. The empirical Bayes procedure shrinks multiple dispersion-related parameters. Shrinkage leads to more stable estimates of the model parameters, better control of false positives and improvement of reproducibility. In addition, to make estimates of the DNA copy number more stable, model parameters are also estimated in a multivariate way using triplets of features, imposing a spatial prior for the copy number effect.Conclusion
With the proposed method for analysis of time-course multilevel molecular data, more profound insight may be gained through the identification of temporal differential expression induced by DNA copy number abnormalities. In particular, in the analysis of an integrative oncogenomics study with a time-course set-up our method finds genes previously reported to be involved in cervical carcinogenesis. Furthermore, the proposed method yields improvements in sensitivity, specificity and reproducibility compared to existing methods. Finally, the proposed method is able to handle count (RNAseq) data from time course experiments as is shown on a real data set.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-327) contains supplementary material, which is available to authorized users. 相似文献57.
Penning TD Chandrakumar NS Desai BN Djuric SW Gasiecki AF Malecha JW Miyashiro JM Russell MA Askonas LJ Gierse JK Harding EI Highkin MK Kachur JF Kim SH Villani-Price D Pyla EY Ghoreishi-Haack NS Smith WG 《Bioorganic & medicinal chemistry letters》2003,13(6):1137-1139
The synthesis and biological evaluation of a series of heterocyclic analogues of the previously reported LTA(4) hydrolase inhibitor 1b are described. Imidazopyridine and purine analogues are specifically highlighted with several demonstrating excellent potency in our in vitro assays, as well as good oral activity in a mouse ex vivo assay. 相似文献
58.
Pesic S Jakovljevic V Djordjevic D Cubrilo D Zivkovic V Jorga V Mujovic V Djuric D Stojimirovic B 《The Chinese journal of physiology》2012,55(1):8-15
Regular training has been claimed to increase the activity of antioxidant enzymes and, consequently, augments the resistance to oxidative stress; however, large volumes of training performed by elite sportsmen could lead to a chronic oxidative stress state. The aim of our study was to assess the oxidative status of elite athletes at the beginning of the preparatory and the beginning of the competition training phases, so that the influence of three months of programmed physical activity on redox status could be determined. The chronic effects of exercise on the redox state of the athletes were compared to the effects of a single bout of karate training. Thirty elite karate athletes, 16-30 years old, were subjected to maximal graded exercise test to estimate their aerobic capacity; blood sampling was also performed to measure levels of superoxide anion radical (O??), hydrogen peroxide (H?O?), superoxide dismutase activity (SOD) and catalase activity (CAT). The only significant change after the three-month training process was found in the significantly decreased CAT activity (X ± SE: 7.95 ± 0.13 U/g Hb × 103 in the preparatory period, 6.65 ± 0.28 U/g Hb × 103 in the competition stage; P < 0.01). After a single karate training session, there was statistically significant decrease of O??(X ± SE: 32.7 ± 4.9 nmol/ml in the preparatory period, 24.5 ± 2.5 nmol/ml in the competition stage; P < 0.05) and increase of H?O?(X ± SE: 11.8 ± 1.0 nmol/ml in the preparatory period, 14.2 ± 0.9 nmol/ml in the competition stage; P < 0.01), as well as significant CAT increase (X ± SE: 6.6 ± 0.6 U/g Hb × 103 in the preparatory period, 8.5 ± 0.5 U/g Hb × 103 in the competition stage; P < 0.05). Although the three-month training process induced, at the first sight, negative changes in the redox state, expressed through the decrease in CAT activity, adequate response of the antioxidant system of our athletes to acute exercise was preserved. 相似文献
59.
Liu Y Donner PL Pratt JK Jiang WW Ng T Gracias V Baumeister S Wiedeman PE Traphagen L Warrior U Maring C Kati WM Djuric SW Molla A 《Bioorganic & medicinal chemistry letters》2008,18(11):3173-3177
Halosalicylamide derivatives were identified from high-throughput screening as potent inhibitors of HCV NS5B polymerase. The subsequent structure and activity relationship revealed the absolute requirement of the salicylamide moiety for optimum activity. Methylation of either the hydroxyl group or the amide group of the salicylamide moiety abolished the activity while the substitutions on both phenyl rings are acceptable. The halosalicylamide derivatives were shown to be non-competitive with respect to elongation nucleotide and demonstrated broad genotype activity against genotype 1-3 HCV NS5B polymerases. Inhibitor competition studies indicated an additive binding mode to the initiation pocket that is occupied by the thiadiazine class of compounds and an additive binding mode to the elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase. 相似文献
60.
Region‐dependent patterns of trabecular bone growth in the human proximal femur: A study of 3D bone microarchitecture from early postnatal to late childhood period
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