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891.
Ali G Lee K Andrade PB Basit S Santos-Cortez RL Chen L Jelani M Ansar M Ahmad W Leal SM 《Human heredity》2011,71(2):106-112
A novel locus DFNB90 was mapped to 7p22.1-p15.3 by carrying out a genome scan in a multigenerational consanguineous family from Pakistan with autosomal recessive nonsyndromic hearing impairment (ARNSHI).DFNB90 is the eighth ARNSHI locus mapped to chromosome 7. A multipoint LOD score of 4.0 was obtained at a number of SNP marker loci spanning from rs1468996 (chromosome 7: 5.7 Mb) tors957960 (chromosome 7: 18.8 Mb). The 3-unit support interval and the region of homozygosity for DFNB90 spans from markers rs1553960 (chromosome 7: 4.9 Mb) to rs206198 (chromosome 7: 20.3 Mb). Candidate genes ACTB, BZW, OCM, MACC1, NXPH1, PRPS1L1, RAC1 and RPA3, which lie within the DFNB90 region, were sequenced and no potentially causal variants were identified. 相似文献
892.
Lorenzen I Trad A Grötzinger J 《Biochemical and biophysical research communications》2011,(2):330-336
A disintegrin and metalloprotease protein 17 (ADAM17) is a transmembrane zinc dependent metalloprotease. The catalytic activity of the enzyme results in the shedding of a broad range of membrane proteins. The release of the corresponding ectodomains induces a switch in various physiological and pathophysiological processes. So far there is not much information about the molecular mechanism of ADAM17 activation available. As for other transmembrane proteases, multimerisation may play a critical role in the activation and function of ADAM17. The present work demonstrates that ADAM17 indeed exists as a multimer in the cell membrane and that this multimerisation is mediated by its EGF-like domain. 相似文献
893.
Saheem Ahmad Moinuddin Kiran Dixit Uzma Shahab Khursheed Alam Asif Ali 《Biochemical and biophysical research communications》2011,407(3):568
The highly reactive electrophile, methylglyoxal (MG), a break down product of carbohydrates, is a major environmental mutagen having potential genotoxic effects. Previous studies have suggested the reaction of MG with free amino groups of proteins forming advanced glycation end products (AGEs). This results in the generation of free radicals which play an important role in pathophysiology of aging and diabetic complications. MG also reacts with free amino group of nucleic acids resulting in the formation of DNA–AGEs. While the formation of nucleoside AGEs has been demonstrated previously, no extensive studies have been performed to assess the genotoxicity and immunogenicity of DNA–AGEs. In this study we report both the genotoxicity and immunogenicity of AGEs formed by MG–Lys–Cu2+ system. Genotoxicity of the experimentally generated AGEs was confirmed by comet-assay. Spectroscopical analysis and melting temperature studies suggest structural perturbations in the DNA as a result of modification. This might be due to generation of single-stranded regions and destabilization of hydrogen bonds. Immunogenicity of native and MG–Lys–Cu2+-DNA was probed in female rabbits. The modified DNA was highly immunogenic eliciting high titre immunogen specific antibodies, while the unmodified form was almost non-immunogenic. The results show structural perturbations in MG–Lys–Cu2+-DNA generating new epitopes that render the molecule immunogenic. 相似文献
894.
We have employed a rapid fluorescence-based screen to assess the polyspecificity of several aminoacyl-tRNA synthetases (aaRSs) against an array of unnatural amino acids. We discovered that a p-cyanophenylalanine specific aminoacyl-tRNA synthetase (pCNF-RS) has high substrate permissivity for unnatural amino acids, while maintaining its ability to discriminate against the 20 canonical amino acids. This orthogonal pCNF-RS, together with its cognate amber nonsense suppressor tRNA, is able to selectively incorporate 18 unnatural amino acids into proteins, including trifluoroketone-, alkynyl-, and halogen-substituted amino acids. In an attempt to improve our understanding of this polyspecificity, the X-ray crystal structure of the aaRS-p-cyanophenylalanine complex was determined. A comparison of this structure with those of other mutant aaRSs showed that both binding site size and other more subtle features control substrate polyspecificity. 相似文献
895.
Lin AP Demeler B Minard KI Anderson SL Schirf V Galaleldeen A McAlister-Henn L 《Biochemistry》2011,50(2):230-239
Yeast NAD(+)-specific isocitrate dehydrogenase (IDH) is an octameric enzyme composed of four heterodimers of regulatory IDH1 and catalytic IDH2 subunits. The crystal structure suggested that the interactions between tetramers in the octamer are restricted to defined regions in IDH1 subunits from each tetramer. Using truncation and mutagenesis, we constructed three tetrameric forms of IDH. Truncation of five residues from the amino terminus of IDH1 did not alter the octameric form of the enzyme, but this truncation with an IDH1 G15D or IDH1 D168K residue substitution produced tetrameric enzymes as assessed by sedimentation velocity ultracentrifugation. The IDH1 G15D substitution in the absence of any truncation of IDH1 was subsequently found to be sufficient for production of a tetrameric enzyme. The tetrameric forms of IDH exhibited ~50% reductions in V(max) and in cooperativity with respect to isocitrate relative to those of the wild-type enzyme, but they retained the property of allosteric activation by AMP. The truncated (-5)IDH1/IDH2 and tetrameric enzymes were much more sensitive than the wild-type enzyme to inhibition by the oxidant diamide and concomitant formation of a disulfide bond between IDH2 Cys-150 residues. Binding of ligands reduced the sensitivity of the wild-type enzyme to diamide but had no effect on inhibition of the truncated or tetrameric enzymes. These results suggest that the octameric structure of IDH has in part evolved for regulation of disulfide bond formation and activity by ensuring the proximity of the amino terminus of an IDH1 subunit of one tetramer to the IDH2 Cys-150 residues in the other tetramer. 相似文献
896.
Shin YS Remacle F Fan R Hwang K Wei W Ahmad H Levine RD Heath JR 《Biophysical journal》2011,(10):2378-2386
Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,···), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network. 相似文献
897.
898.
899.
Moradi AB Carminati A Vetterlein D Vontobel P Lehmann E Weller U Hopmans JW Vogel HJ Oswald SE 《The New phytologist》2011,192(3):653-663
? Despite the importance of rhizosphere properties for water flow from soil to roots, there is limited quantitative information on the distribution of water in the rhizosphere of plants. ? Here, we used neutron tomography to quantify and visualize the water content in the rhizosphere of the plant species chickpea (Cicer arietinum), white lupin (Lupinus albus), and maize (Zea mays) 12 d after planting. ? We clearly observed increasing soil water contents (θ) towards the root surface for all three plant species, as opposed to the usual assumption of decreasing water content. This was true for tap roots and lateral roots of both upper and lower parts of the root system. Furthermore, water gradients around the lower part of the roots were smaller and extended further into bulk soil compared with the upper part, where the gradients in water content were steeper. ? Incorporating the hydraulic conductivity and water retention parameters of the rhizosphere into our model, we could simulate the gradual changes of θ towards the root surface, in agreement with the observations. The modelling result suggests that roots in their rhizosphere may modify the hydraulic properties of soil in a way that improves uptake under dry conditions. 相似文献
900.
A study was undertaken to investigate the presence of archaeal diversity in saltpan sediments of Goa, India by 16S rDNA-dependent
molecular phylogeny. Small subunit rRNA (16S rDNA) from saltpan sediment metagenome were amplified by polymerase chain reaction
(PCR) using primers specific to the domain archaea. 10 unique phylotypes were obtained by PCR based RFLP of 16S rRNA genes
using endonuclease Msp 1, which was most suitable to score the genetic diversity. These phylotypes spanned a wide range within the domain archaea
including both crenarchaeota and euryarcheaota. None of the retrieved crenarchaeota sequences could be grouped with previously
cultured crenarchaeota however; two sequences were related with haloarchaea. Most of the sequences determined were closely
related to the sequences that had been previously obtained from metagenome of a variety of marine environments. The phylogenetic
study of a site investigated for the first time revealed the presence of low archaeal population but showed yet unclassified
species, may specially adapted to the salt pan sediment of Goa. 相似文献