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281.
Çakmak R Durdagi S Ekinci D Sentürk M Topal G 《Bioorganic & medicinal chemistry letters》2011,21(18):5398-5402
Discovery of GR inhibitors has become very popular recently due to antimalarial and anticancer activities. In this study, the synthesis and GR inhibitory capacities of novel nitroaromatic compounds (NCs) (1-3) were reported. Some commercially available molecules were also tested for comparison reasons. The novel NCs were obtained in high yields using simple chemical procedures and exhibited much potent inhibitory activities against GR at low micromolar concentrations with K(i) values ranging from 0.211 to 4.57 μM as compared with well-known agents. Inhibition mechanism was assessed as being due to occlusion of the active site entrance by means of the NCs. Molecular docking results have shown that docking poses of ligands are able to construct binding interactions with the essential amino acids. 相似文献
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283.
Pastural E Ersoy F Yalman N Wulffraat N Grillo E Ozkinay F Tezcan I Gediköglu G Philippe N Fischer A de Saint Basile G 《Genomics》2000,63(3):299-306
Griscelli syndrome is a rare autosomal recessive disease characterized by pigment dilution, variable cellular immunodeficiency, and an acute phase of uncontrolled T lymphocyte and macrophage activation. We previously mapped the disease locus to 15q21 and showed that a MyoVa gene (HGMW-approved symbol MYO5A) defect leads to Griscelli syndrome. We report a second MyoVa mutation in a new patient, confirming this first finding. However, in four other Griscelli syndrome patients analyzed, the MYOVA protein is expressed, and no mutation can be detected in the MyoVa gene coding sequence, even in the alternatively spliced region for which exon-intron boundaries were characterized. Linkage analysis performed in 15 Griscelli families thus far studied confirms the first localization. However, fine haplotype analysis in three families strongly suggests the existence of a second gene at the same locus for Griscelli syndrome less than 7.3 cM distant from the MyoVa gene. 相似文献
284.
Contribution to the taxonomy of Turkish Scorzonera (Asteraceae) taxa based on vegetative anatomy
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Serdar Makbul Kamil Coşkunçelebi Seda Okur Mutlu Gültepe 《Nordic Journal of Botany》2016,34(6):670-684
In the present study, the general stem, root and leaf anatomical features of 59 Scorzonera L. s.l. (Asteraceae) taxa collected from Turkey are presented and evaluated by cluster and principal coordinate analysis. Numerical analyses based on 26 anatomical traits showed that arrangement of tracheal elements in the root, presence of cortical bundles, latex canals, secretory cells and aerenchyma in the stem and mesophyll are valuable for grouping Scorzonera taxa. Dendograms inferred from anatomical data were generally congruent with the traditional subgeneric classification of Scorzonera (Scorzonera L., Podospermum DC., Pseudopodospermum (Lipsch. et Krasch.) Lipsch.). However, the present study also show that the examined species may not be identified only based on the internal morphology of root, stem and leaf. In addition, the results support to treat Podospermum as a distinct genus. 相似文献
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286.
Elizabeth A. Best Elizabeth Juarez-Colunga Katherine James William G. LeBlanc Berrin Serdar 《PloS one》2016,11(2)
Recent studies report a link between common environmental exposures, such as particulate matter air pollution and tobacco smoke, and decline in cognitive function. The purpose of this study was to assess the association between exposure to polycyclic aromatic hydrocarbons (PAHs), a selected group of chemicals present in particulate matter and tobacco smoke, and measures of cognitive performance among elderly in the general population. This cross-sectional analysis involved data from 454 individuals aged 60 years and older from the 2001–2002 National Health and Nutrition Examination Survey. The association between PAH exposures (as measured by urinary biomarkers) and cognitive function (digit symbol substitution test (DSST)) was assessed using multiple linear regression analyses. After adjusting for age, socio-economic status and diabetes we observed a negative association between urinary 1-hydroxypyrene, the gold standard of PAH exposure biomarkers, and DSST score. A one percent increase in urinary 1-hydroxypyrene resulted in approximately a 1.8 percent poorer performance on the digit symbol substitution test. Our findings are consistent with previous publications and further suggest that PAHs, at least in part may be responsible for the adverse cognitive effects linked to tobacco smoke and particulate matter air pollution. 相似文献
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Ramin?Ekhteiari Salmas Mert Mestanoglu Mine Yurtsever Sergei?Y. Noskov Serdar Durdagi 《Biophysical journal》2015,109(6):1163-1168
PDEδ is a small protein that binds and controls the trafficking of RAS subfamily proteins. Its inhibition protects initiation of RAS signaling, and it is one of the common targets considered for oncological drug development. In this study, we used solved x-ray structures of inhibitor-bound PDEδ targets to investigate mechanisms of action of six independent all-atom MD simulations. An analysis of atomic simulations combined with the molecular mechanic-Poisson-Boltzmann solvent accessible surface area/generalized Born solvent accessible surface area calculations led to the identification of action mechanisms for a panel of novel PDEδ inhibitors. To the best of our knowledge, this study is one of the first in silico investigations on co-crystallized PDEδ protein. A detailed atomic-scale understanding of the molecular mechanism of PDEδ inhibition may assist in the design of novel PDEδ inhibitors. One of the most common side effects for diverse small molecules/kinase inhibitors is their off-target interactions with cardiac ion channels and human-ether-a-go-go channel specifically. Thus, all of the studied PDEδ inhibitors are also screened in silico at the central cavities of hERG1 potassium channels. 相似文献
289.
Unlü S Banoglu E Ito S Niiya T Eren G Okçelik B Sahin MF 《Journal of enzyme inhibition and medicinal chemistry》2007,22(3):351-361
In a search for novel compounds with analgesic and anti-inflammatory activity, a series of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole (5a-f, 6a-f) and 1-(3-pyridazinyl)-5-arylpyrazole (7a-f, 8a-f) derivatives were synthesized. The structure of these regioisomers was confirmed by spectral techniques. The compounds were preliminarily screened at 8 microM concentration for their inhibitory activity against cyclooxygenase enzymes, COX-1 and COX-2, using a human whole blood test. The tested derivatives showed inhibitory activity for both enzymes and are worthy of further investigation for developing better leads. 相似文献
290.
Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells 总被引:1,自引:0,他引:1
Velmurugan K Chen B Miller JL Azogue S Gurses S Hsu T Glickman M Jacobs WR Porcelli SA Briken V 《PLoS pathogens》2007,3(7):e110
The survival and persistence of Mycobacterium tuberculosis depends on its capacity to manipulate multiple host defense pathways, including the ability to actively inhibit the death by apoptosis of infected host cells. The genetic basis for this anti-apoptotic activity and its implication for mycobacterial virulence have not been demonstrated or elucidated. Using a novel gain-of-function genetic screen, we demonstrated that inhibition of infection-induced apoptosis of macrophages is controlled by multiple genetic loci in M. tuberculosis. Characterization of one of these loci in detail revealed that the anti-apoptosis activity was attributable to the type I NADH-dehydrogenase of M. tuberculosis, and was mainly due to the subunit of this multicomponent complex encoded by the nuoG gene. Expression of M. tuberculosis nuoG in nonpathogenic mycobacteria endowed them with the ability to inhibit apoptosis of infected human or mouse macrophages, and increased their virulence in a SCID mouse model. Conversely, deletion of nuoG in M. tuberculosis ablated its ability to inhibit macrophage apoptosis and significantly reduced its virulence in mice. These results identify a key component of the genetic basis for an important virulence trait of M. tuberculosis and support a direct causal relationship between virulence of pathogenic mycobacteria and their ability to inhibit macrophage apoptosis. 相似文献