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51.
Jigme M Sethi Augustine MK Choi William J Calhoun Bill T Ameredes 《Respiratory research》2008,9(1):45
Background
Nitric oxide (NO) and carbon monoxide (CO) in exhaled breath are considered obtainable biomarkers of physiologic mechanisms. Therefore, obtaining their measures simply, non-invasively, and repeatedly, is of interest, and was the purpose of the current study.Methods
Expired NO (ENO) and CO (ECO) were measured non-invasively using a gas micro-analyzer on several strains of mice (C57Bl6, IL-10-/-, A/J, MKK3-/-, JNK1-/-, NOS-2-/- and NOS-3-/-) with and without allergic airway inflammation (AI) induced by ovalbumin systemic sensitization and aerosol challenge, compared using independent-sample t-tests between groups, and repeated measures analysis of variance (ANOVA) within groups over time of inflammation induction. ENO and ECO were also measured in C57Bl6 and IL-10-/- mice, ages 8–58 weeks old, the relationship of which was determined by regression analysis. S-methionyl-L-thiocitrulline (SMTC), and tin protoporphyrin (SnPP) were used to inhibit neuronal/constitutive NOS-1 and heme-oxygenase, respectively, and alter NO and CO production, respectively, as assessed by paired t-tests. Methacholine-associated airway responses (AR) were measured by the enhanced pause method, with comparisons by repeated measures ANOVA and post-hoc testing.Results
ENO was significantly elevated in naïve IL-10-/- (9–14 ppb) and NOS-2-/- (16 ppb) mice as compared to others (average: 5–8 ppb), whereas ECO was significantly higher in naïve A/J, NOS-3-/- (3–4 ppm), and MKK3-/- (4–5 ppm) mice, as compared to others (average: 2.5 ppm). As compared to C57Bl6 mice, AR of IL-10-/-, JNK1-/-, NOS-2-/-, and NOS-3-/- mice were decreased, whereas they were greater for A/J and MKK3-/- mice. SMTC significantly decreased ENO by ~30%, but did not change AR in NOS-2-/- mice. SnPP reduced ECO in C57Bl6 and IL-10-/- mice, and increased AR in NOS-2-/- mice. ENO decreased as a function of age in IL-10-/- mice, remaining unchanged in C57Bl6 mice.Conclusion
These results are consistent with the ideas that: 1) ENO is associated with mouse strain and knockout differences in NO production and AR, 2) alterations of ENO and ECO can be measured non-invasively with induction of allergic AI or inhibition of key gas-producing enzymes, and 3) alterations in AR may be dependent on the relative balance of NO and CO in the airway. 相似文献52.
Biomarkers aid the study of osteoarthritis (OA) in a number of different ways. In this article we summarise briefly their
multiple uses and reflect on how the study reported in a previous edition of Arthritis Research & Therapy should promote further investigation of cartilage oligomeric matrix protein (COMP). COMP is foremost among hitherto investigated
biomarkers and is most consistently shown to predict knee OA progression. Precisely what role it plays in OA pathogenesis
remains unclear and elucidating this may be key to defining, and then targeting, the cellular pathways involved in OA. 相似文献
53.
Khajeddin SJ Akbari M Karimzadeh HR Eghbal MK 《植物生态学报》2008,32(2):328-335
Aims Desertification results in ecological and biological diminution of the earth, and can happen naturally or cause by anthropogenic activities. This process especially affects arid and semi-arid regions, such as the Isfahan region, where the spread of desertification is reaching critical proportions. The aim of this study is to use remotely sensed data to review the trend of desertification in the northern of Isfahan, Iran. Methods Multi-temporal images were employed to evaluate the trend of desertification, specifically the TM and ETM+ data of September, 1990 and September, 2001. Geometric and radiometric corrections were applied to each image prior to image processing and supervised classification, and vegetation indices were applied to produce a land use map of each image in nine classes. The land use classification s in the two map images were compared and changes between land use classes were detected over the 11 year period using a fuzzy and post-classification technique. Important findings The maps and their comparison with false color composite images showed the differences efficiently. With the fuzzy and post-classification method the land use changes were sited on the map. Fuzzy confirmed 53% changed area and 47% unchanged areas in the study region. The results verify the desertification expansion in the study areas. Because of poor land management, agricultural lands converted to desert and abandoned areas, and some marginal pasture lands had to be changed to agricultural land which are desertification spreading according to United Nations Conference on Desertification (UNCOD). Also farmland and pastures have been converted to urban and industrial areas, and the rangelands have been spoiled due to opencast mine excavations. With the mine margins eroding as well as their debris accumulating on the pasture lands, desertification has become worse. Three areas of less-elevated mountains have remained unchanged. This study confirmed that the anthropogenic activities accelerated the desertification process and severely endangered the remaining areas. 相似文献
54.
Background
There are two different theories about the development of the genetic code. Woese suggested that it was developed in connection with the amino acid repertoire, while Crick argued that any connection between codons and amino acids is only the result of an "accident". This question is fundamental to understand the nature of specific protein-nucleic acid interactions. 相似文献55.
Binding to serine 65‐phosphorylated ubiquitin primes Parkin for optimal PINK1‐dependent phosphorylation and activation
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Agne Kazlauskaite R Julio Martínez‐Torres Scott Wilkie Atul Kumar Julien Peltier Alba Gonzalez Clare Johnson Jinwei Zhang Anthony G Hope Mark Peggie Matthias Trost Daan MF van Aalten Dario R Alessi Alan R Prescott Axel Knebel Helen Walden Miratul MK Muqit 《EMBO reports》2015,16(8):939-954
Mutations in the mitochondrial protein kinase PINK1 are associated with autosomal recessive Parkinson disease (PD). We and other groups have reported that PINK1 activates Parkin E3 ligase activity both directly via phosphorylation of Parkin serine 65 (Ser65)—which lies within its ubiquitin‐like domain (Ubl)—and indirectly through phosphorylation of ubiquitin at Ser65. How Ser65‐phosphorylated ubiquitin (ubiquitinPhospho‐Ser65) contributes to Parkin activation is currently unknown. Here, we demonstrate that ubiquitinPhospho‐Ser65 binding to Parkin dramatically increases the rate and stoichiometry of Parkin phosphorylation at Ser65 by PINK1 in vitro. Analysis of the Parkin structure, corroborated by site‐directed mutagenesis, shows that the conserved His302 and Lys151 residues play a critical role in binding of ubiquitinPhospho‐Ser65, thereby promoting Parkin Ser65 phosphorylation and activation of its E3 ligase activity in vitro. Mutation of His302 markedly inhibits Parkin Ser65 phosphorylation at the mitochondria, which is associated with a marked reduction in its E3 ligase activity following mitochondrial depolarisation. We show that the binding of ubiquitinPhospho‐Ser65 to Parkin disrupts the interaction between the Ubl domain and C‐terminal region, thereby increasing the accessibility of Parkin Ser65. Finally, purified Parkin maximally phosphorylated at Ser65 in vitro cannot be further activated by the addition of ubiquitinPhospho‐Ser65. Our results thus suggest that a major role of ubiquitinPhospho‐Ser65 is to promote PINK1‐mediated phosphorylation of Parkin at Ser65, leading to maximal activation of Parkin E3 ligase activity. His302 and Lys151 are likely to line a phospho‐Ser65‐binding pocket on the surface of Parkin that is critical for the ubiquitinPhospho‐Ser65 interaction. This study provides new mechanistic insights into Parkin activation by ubiquitinPhospho‐Ser65, which could aid in the development of Parkin activators that mimic the effect of ubiquitinPhospho‐Ser65. 相似文献
56.
Differential genome analyses of metabolic enzymes in Pseudomonas aeruginosa for drug target identification 总被引:1,自引:0,他引:1
Complete genome sequences of several pathogenic bacteria have been determined, and many more such projects are currently under way. While these data potentially contain all the determinants of host-pathogen interactions and possible drug targets, computational tools for selecting suitable candidates for further experimental analyses are currently limited. Detection of bacterial genes that are non-homologous to human genes, and are essential for the survival of the pathogen represents a promising means of identifying novel drug targets. We used a differential pathway analyses approach (based on KEGG data) to identify essential genes from Pseudomonas aeruginosa. Our approach identified 214 unique enzymes in P. aeruginosa that may be potential drug targets and can be considered for rational drug design. About 40% of these putative targets have been reported as essential by transposon mutagenesis data elsewhere. Homology model for one of the proteins (LpxC) is presented as a case study and can be explored for in silico docking with suitable inhibitors. This approach is a step towards facilitating the search for new antibiotics. 相似文献
57.
在韩国境内Potentilla fragarioides var.sprengeliana的遗传多样 … 总被引:1,自引:0,他引:1
根据22个等位酶位点遗传变异,探讨了韩国境内委陵菜(Potentilla fragarioides L.var.sprengeliana)的遗传多样性和种群结构。酶位点的多态位点百分比为59.1%。种和种群水平上的遗传多样性比较高,分别为Hes=0.210,Hep=0.199;而种群的分化水平则相对较低(GST=0.074)。19个种群中随机交配的偏差为FIS=0.331。每代迁移数的间接估计 相似文献
58.
Protein lengths vary considerably from a few to thousands of amino acids and length variations are documented to have multiple effects. A computational approach to investigate the functional impact of protein length variation in genetic disorders is presented. The genes for huge proteins are found to have more introns. Our analysis also shows greater involvement of huge proteins in hereditary diseases. 相似文献
59.
60.
Insight into gene fusion from molecular dynamics simulation of fused and un-fused IGPS (Imidazole Glycerol Phosphate Synthetase)
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Gene fusion produces proteins with novel structural architectures during evolution. Recent comparative genome analysis shows several cases of fusion/fission across distant phylogeny. However, the selection forces driving gene fusion are not fully understood due to the lack of structural, dynamics and kinetics data. Available structural data at PDB (protein databank) contains limited cases of structural pairs describing fused and un-fused structures. Nonetheless, we identified a pair of IGPS (imidazole glycerol phosphate synthetase) structures (comprising of HisF - glutaminase unit and HisH - cyclase unit) from S. cerevisiae (SC) and T. thermophilus (TT). The HisF-HisH structural units are domains in SC and subunits in TT. Hence, they are fused in SC and un-fused in TT. Subsequently, a domain-domain interface is formed in SC and a subunit-subunit interface in TT between HisF and HisH. Our interest is to document the structure and dynamics differences between fused and un-fused IGPS. Therefore, we probed into the structures of fused IGPS in SC and un-fused IGPS in TT using molecular dynamics simulation for 5ns. Simulation shows that fused IGPS in SC has larger interface area between HisF-HisH and greater radius of gyration compared to un-fused IGPS in TT. These structural features for the first time demonstrate the evolutionary advantage in generating proteins with novel structural architecture through gene fusion. 相似文献