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61.
Crystals of ribosomal protein L6 from Bacillus stearothermophilus suitable for high resolution structural studies have been obtained. Crystals are hexagonal with space group P6122 (or the enantiomorph P6522) and cell dimensions a = b = 72.7 Å, c = 124.9 Å. A search for heavy atom derivatives is in progress. 相似文献
62.
Otylia Kowal-Bielecka Marek Bielecki Serena Guiducci Beata Trzcinska-Butkiewicz Ma?gorzata Michalska-Jakubus Marco Matucci-Cerinic Marek Brzosko Dorota Krasowska Lech Chyczewski Krzysztof Kowal 《Arthritis research & therapy》2013,15(3):R69
Introduction
Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. CD163 is a scavenger receptor which affects inflammatory response and may contribute to connective tissue remodelling. It has recently been demonstrated that CD163 can bind and neutralize the TNF-like weak inducer of apoptosis (TWEAK), a multifunctional cytokine which regulates inflammation, angiogenesis and tissue remodelling. We aimed to investigate the relationships between serum levels of soluble CD163 (sCD163) and soluble TWEAK (sTWEAK) in relation to disease manifestations in SSc patients.Methods
This study included 89 patients with SSc who had not received immunosuppressive drugs or steroids for at least 6 months and 48 age- and sex-matched healthy controls (HC) from four European centres. Serum concentrations of sTWEAK and sCD163 were measured using commercially available ELISA kits.Results
The mean serum concentrations of sTWEAK were comparable between SSc patients (mean +/- SD: 270 +/- 171 pg/mL) and HC (294 +/- 147pg/mL, P >0.05). Concentration of sCD163 and sCD163/sTWEAK ratio were significantly greater in SSc patients (984 +/- 420 ng/mL and 4837 +/- 3103, respectively) as compared to HC (823 +/- 331 ng/mL and 3115 +/- 1346 respectively, P <0.05 for both). High sCD163 levels and a high sCD163/sTWEAK ratio (defined as > mean +2SD of HC) were both associated with a lower risk of digital ulcers in SSc patients (OR, 95%CI: 0.09; 0.01, 0.71, and 0.17; 0.06, 0.51, respectively). Accordingly, patients without digital ulcers had a significantly higher sCD163 concentration and sCD163/sTWEAK ratio as compared to SSc patients with digital ulcers (P <0.01 for both) and HC (P <0.05 for both). A high sCD163/sTWEAK ratio, but not high sCD163 levels, was associated with greater skin involvement.Conclusions
The results of our study indicate that CD163-TWEAK interactions might play a role in the pathogenesis of SSc and that CD163 may protect against the development of digital ulcers in SSc. Further studies are required to reveal whether targeting of the CD163-TWEAK pathway might be a potential strategy for treating vascular disease and/or skin fibrosis in SSc. 相似文献63.
Izabela Chojnicka Krzysztof Gajos Katarzyna Strawa Gra?yna Broda Sylwia Fudalej Marcin Fudalej Piotr Stawiński Aleksandra Pawlak Pawe? Krajewski Marcin Wojnar Rafa? P?oski 《PloS one》2013,8(2)
Background
rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide.Methods
We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians.Results
We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR = 1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019).Conclusions
In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol. 相似文献64.
Krzysztof Mikołajczak Anetta Kuczyńska Paweł Krajewski Aneta Sawikowska Maria Surma Piotr Ogrodowicz Tadeusz Adamski Karolina Krystkowiak Andrzej G. Górny Michał Kempa Iwona Szarejko Justyna Guzy-Wróbelska Kornelia Gudyś 《Journal of applied genetics》2017,58(1):23-35
High-yielding capacity of the modern barley varieties is mostly dependent on the sources of semi-dwarfness associated with the sdw1/denso locus. The objective of the study was to identify quantitative trait loci (QTLs) associated with the plant height and yield potential of barley recombinant inbred lines (RILs) grown under various soil moisture regimes. The plant material was developed from a hybrid between the Maresi (European cv.) and CamB (Syrian cv.). A total of 103 QTLs affecting analysed traits were detected and 36 of them showed stable effects over environments. In total, ten QTLs were found to be significant only under water shortage conditions. Nine QTLs affecting the length of main stem were detected on 2H-6H chromosomes. In four of the detected QTLs, alleles contributed by Maresi had negative effects on that trait, the most significant being the QLSt-3H.1-1 in the 3H.1 linkage group. The close linkage between QTLs identified around the sdw1/denso locus, with positive alleles contributed by Maresi, indicates that the semi-dwarf cv. Maresi could serve as a donor of favourable traits resulting in grain yield improvement, also under water scarcity. Molecular analyses revealed that the Syrian cv. also contributed alleles which increased the yield potential. Available barley resources of genomic annotations were employed to the biological interpretation of detected QTLs. This approach revealed 26 over-represented Gene Ontology terms. In the projected support intervals of QGWSl-5H.3-2 and QLSt-5H.3 on the chromosome 5H, four genes annotated to ‘response to stress’ were found. It suggests that these QTL-regions may be involved in a response of plant to a wide range of environmental disturbances. 相似文献
65.
Visfatin levels do not change after the oral glucose tolerance test and after a dexamethasone-induced increase in insulin resistance in humans 总被引:1,自引:0,他引:1
Marcinkowska M Lewandowski KC Lewiński A Bieńkiewicz M Basińska-Lewandowska M Salata I Randeva HS 《Endokrynologia Polska》2007,58(3):188-194
INTRODUCTION, MATERIAL AND METHODS: Visfatin is a cytokine, mainly expressed in visceral fat, that exerts insulin-mimicking effects in rodents through activation of an insulin receptor, although the binding-site is distinct from that of insulin. However, the mechanisms that regulate visfatin synthesis are still not fully understood. In particular, it is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as a glucocorticoid-induced increase in insulin resistance are reflected in appreciable alterations in serum visfatin levels in humans. In order to investigate this we measured serum visfatin, glucose and insulin concentrations during a 75.0 gram oral glucose tolerance test (OGTT) [Study 1], as well as before and after oral administration of dexamethasone [Study 2]. Study 1 included 17 subjects (2 males), aged 35.7 +/- 15.6 (mean +/- SD) years of BMI 35.2 +/- 9.3 kg/m(2). Blood samples were taken before (0 minutes) and at 60 and 120 minutes after glucose administration. Study 2 included 20 subjects (4 males, 5 subjects with type 2 diabetes), aged 42.1 +/- 17.2 years of BMI 36.7 +/- 8.38 kg/m(2) who underwent screening for Cushing's disease/syndrome. Dexamethasone was administered at a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of visfatin, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). Insulin resistance was assessed according to the HOMA method in non-diabetic individuals (n = 15). RESULTS: In Study 1 two subjects were found to have impaired glucose tolerance and one subject was found to have diabetes mellitus. Glucose administration resulted in a highly significant increase in insulin (from 11.4 +/- 7.2 microU/mL at 0 min to 98.9 +/- 68.6 microU/mL at 60 min and 72.6 +/- 45.1 microU/mL at 120 minute of OGTT, p < 0.001 for 60 and 120 minutes in comparison to baseline). However, there was no change in serum visfatin concentrations (84.6 +/- 11.6 ng/mL at 0 minutes, 82.6 +/- 12.7 ng/mL at 60 minutes and 81.1 +/- 14.5 ng/mL at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol concentrations below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.5 +/- 6.9 to 16.9 +/- 7.6 microU/mL; p = 0.011) and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), albeit without a significant change in serum visfatin concentrations (61.1 +/- 19.8 vs. 68.3 +/- 19.4 ng/mL, p = ns). In neither Study 1 nor Study 2 was there any significant correlation between serum visfatin and age, BMI or HOMA. CONCLUSIONS: There is a striking difference between the marked rise in insulin concentrations and the lack of change in visfatin concentrations during the oral glucose tolerance test. This implies that it is highly unlikely that visfatin is involved in the short-term regulation of glucose homeostasis in human subjects. Dexamethasone administration (4 mg/48 hours) induces an increase in insulin resistance, although without significant change in serum visfatin concentrations. Therefore in contrast to the in vitro data, short term glucocorticoid administration does not result in appreciable changes in serum levels of this adipocytokine. Furthermore, the results of our study do not support the notion that glucocorticoid-induced insulin resistance is likely to be related to changes in serum concentrations of visfatin. 相似文献
66.
The ribonucleic acids (RNA) form highly folded structures, which behind the helical fragments contain several secondary and tertiary structural motives. All of them have an influence on thermodynamic stability of the RNA. The 5'- and 3'-dangling ends are one of those structural motives, which effect stability of the adjacent helixes. In this paper, we described the influence of 14 different modified nucleotides, placed as 3'-dangling ends, on thermal stability of the RNA duplexes. Collected data demonstrate that: (i) 5-substituents of the uridine have an impact on the 3'-dangling end effect and the largest changes were observed for 5-chloro, bromo and methyl substituents; (ii) position of the methyl group within the uracil residue affect the thermal stability of the duplex; (iii) increasing a size of the heterocycle base placed as the 3'-terminal unpaired nucleotide enhances stabilization of duplexes. 相似文献
67.
Effects of chronic food restriction and treatments with leptin or ghrelin on different reproductive parameters of male rats 总被引:1,自引:0,他引:1
Sirotkin AV Chrenková M Nitrayová S Patras P Darlak K Valenzuela F Pinilla L Tena-Sempere M 《Peptides》2008,29(8):1362-1368
The existence of a close relationship between energy status and reproductive function is well-documented, especially in females, but its underlying mechanisms remain to be fully unfolded. This study aimed to examine the effects of restriction of daily calorie intake, as well as chronic treatments with the metabolic hormones leptin and ghrelin, on the secretion of different reproductive hormones, namely pituitary gonadotropins and prolactin, as well as testosterone, in male rats. Restriction (50%) in daily food intake for 20 days significantly reduced body weight as well as plasma PRL and T levels, without affecting basal LH and FSH concentrations and testicular weight. Chronic administration of leptin to rats fed ad libitum increased plasma PRL levels and decreased circulating T, while it did not alter other hormonal parameters under analysis. In contrast, in rats subjected to 50% calorie restriction, leptin administration increased plasma T levels and reduced testis weight. Conversely, ghrelin failed to induce major hormonal changes but tended to increase testicular weight in fed animals, while repeated ghrelin injections in food-restricted males dramatically decreased plasma LH and T concentrations and reduced testis weight. In sum, we document herein the isolated and combined effects of metabolic stress (50% food restriction) and leptin or ghrelin treatments on several reproductive hormones in adult male rats. Overall, our results further stress the impact and complex way of action of different metabolic cues, such as energy status and key hormones, in reproductive function also in the male. 相似文献
68.
Wysocka M Lesner A Guzow K Mackiewicz L Legowska A Wiczk W Rolka K 《Analytical biochemistry》2008,378(2):208-215
In this study, chemical synthesis of the selective chromogenic/fluorogenic substrates for proteinase 3 is described. The substrates’ sequence was obtained using combinatorial chemistry methods. Deconvolution of the tripeptide library against proteinase 3 with general formula ABZ-X3-X2-X1-ANB-NH2 yielded the active sequence. Selected peptide was further modified on its C terminus to investigate the impact of chromophore moiety modification on enzyme-substrate interaction. To determine specificity, activity of selected substrates was characterized against proteinase 3 and neutrophil elastase. Finally, the peptide ABZ-Tyr-Tyr-Abu-ANB-NH2 displayed the highest value of specificity constant (kcat/KM = 189 × 103 M−1 s−1) for proteinase 3. To the best of our knowledge, this is the first short peptide that undergoes selective proteolysis by proteinase 3 and displays no significant hydrolysis in the presence of human neutrophil elastase and cathepsin G. 相似文献
69.
Data on the morphology of the egg, mature larva (L3) and pupa of Squamapion
elongatum (Germar, 1817) are presented. The development cycle of this species lasts 51–54 days: a 12-day egg period, a 30-day larval period, and a 12-day pupal period, on average. The larvae are attacked by parasitic hymenopterans of the superfamily Chalcidoidea. 相似文献
70.
Dynamics of subgenomic hepatitis C virus replicon RNA levels in Huh-7 cells after exposure to nucleoside antimetabolites 下载免费PDF全文
Stuyver LJ McBrayer TR Tharnish PM Hassan AE Chu CK Pankiewicz KW Watanabe KA Schinazi RF Otto MJ 《Journal of virology》2003,77(19):10689-10694
Treatment with antimetabolites results in chemically induced low nucleoside triphosphate pools and cell cycle arrest in exponentially growing cells. Since steady-state levels of hepatitis C virus (HCV) replicon RNA were shown to be dependent on exponential growth of Huh-7 cells, the effects of antimetabolites for several nucleoside biosynthesis pathways on cell growth and HCV RNA levels were investigated. A specific anti-HCV replicon effect was defined as (i). minimal interference with the exponential cell growth, (ii). minimal reduction in cellular host RNA levels, and (iii). reduction of the HCV RNA copy number per cell compared to that of the untreated control. While most antimetabolites caused a cytostatic effect on cell growth, only inhibitors of the de novo pyrimidine ribonucleoside biosynthesis mimicked observations seen in confluent replicon cells, i.e., cytostasis combined with a sharp decrease in replicon copy number per cell. These results suggest that high levels of CTP and UTP are critical parameters for maintaining the steady-state level replication of HCV replicon in Huh-7 cells. 相似文献