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971.
Rancourt RC Tai S King M Heltshe SL Penvari C Accurso FJ White CW 《American journal of physiology. Lung cellular and molecular physiology》2004,286(5):L931-L938
The persistent and viscous nature of airway secretions in cystic fibrosis (CF) disease leads to airway obstruction, opportunistic infection, and deterioration of lung function. Thioredoxin (Trx) is a protein disulfide reductase that catalyzes numerous thiol-dependent cellular reductive processes. To determine whether Trx can alter the rheological properties of mucus, sputum obtained from CF patients was treated with TRX and its reducing system (0.1 microM thioredoxin reductase + 2 mM NADPH), and liquid phase-gel phase ratio (percent liquid phase) was assessed by compaction assay. Exposure to low Trx concentrations (1 microM) caused significant increases in the percentage of liquid phase of sputum. Maximal increases in percent liquid phase occurred with 30 microM Trx. Additional measurements revealed that sputum liquefaction by the Trx reducing system is dependent on NADPH concentration. The relative potency of the Trx reducing system also was compared with other disulfide-reducing agents. In contrast with Trx, glutathione and N-acetylcysteine were ineffective in liquefying sputum when used at concentrations <1 mM. Sputum viscoelasticity, measured by magnetic microrheometry, also was diminished significantly following 20-min treatment with 3, 10, or 30 microM Trx. Similarly, this reduction in viscoelasticty also was dependent on NADPH concentration. Further investigation has indicated that Trx treatment increases the solubility of high-molecular-weight glycoproteins and causes redistribution of extracellular DNA into the liquid phase of sputum. Recognizing that mucins are the major gel-forming glycoproteins in mucus, we suggest that Trx alters sputum rheology by enzymatic reduction of glycoprotein polymers present in sputum. 相似文献
972.
Adeeb S Ali A Shrive N Frank C Smith D 《Computer methods in biomechanics and biomedical engineering》2004,7(1):33-42
Experimental observations suggest that during a ligament tensile strain test, water and glycosaminoglycans are exuded. Many attempts have been tried to model this behaviour using continuum mechanics. We have investigated this unique behaviour and have established three mechanisms which may contribute to the experimental observations: the slackness of the fibres before stretching can lead to a decrease in volume upon straightening; a Poisson's ratio higher than 0.5 from the axial to the lateral direction (as recorded in the literature [Hewitt, J., Guilak, F., Glisson, R. and Parker Vail, T. (2001) "Regional material properties of the human hip joint capsule ligaments", Journal of Orthopaedic Research 19(3), 359-364]) due to the very high level of anisotropy of the tissue; and an osmotic pressure, with a certain level of anisotropy, that causes the swelling of the tissue before loading [Thornton, G.M., Shrive, N.G. and Frank, C.B. (2001) "Altering ligament water content affects ligament pre-stress and creep behaviour", Journal of Orthopaedic Research 19(5), 845-851]. There may be other mechanisms that also contribute in the observed fluid exudation on tensile loading. 相似文献
973.
A method of supervised classification using two available structure templates was applied to investigate the possible heterogeneity existing in a large cryo-EM dataset of an Escherichia coli 70S ribosome-EF-G complex. Two subpopulations showing the ribosome in distinct conformational states, related by a ratchet-like rotation of the 30S subunit with respect to the 50S subunit, were extracted from the original dataset. The possible presence of additional intermediate states is discussed. 相似文献
974.
975.
Position of single amino acid substitutions in the collagen triple helix determines their effect on structure of collagen fibrils 总被引:4,自引:0,他引:4
Steplewski A Ito H Rucker E Brittingham RJ Alabyeva T Gandhi M Ko FK Birk DE Jimenez SA Fertala A 《Journal of structural biology》2004,148(3):674-337
Collagen II fibrils are a critical structural component of the extracellular matrix of cartilage providing the tissue with its unique biomechanical properties. The self-assembly of collagen molecules into fibrils is a spontaneous process that depends on site-specific binding between specific domains belonging to interacting molecules. These interactions can be altered by mutations in the COL2A1 gene found in patients with a variety of heritable cartilage disorders known as chondrodysplasias. Employing recombinant procollagen II, we studied the effects of R75C or R789C mutations on fibril formation. We determined that both R75C and R789C mutants were incorporated into collagen assemblies. The effects of the R75C and R789C substitutions on fibril formation differed significantly. The R75C substitution located in the thermolabile region of collagen II had no major effect on the fibril formation process or the morphology of fibrils. In contrast, the R789C substitution located in the thermostable region of collagen II caused profound changes in the morphology of collagen assemblies. These results provide a basis for identifying pathways leading from single amino acid substitutions in collagen II to changes in the structure of individual fibrils and in the organization of collagenous matrices. 相似文献
976.
Yeast lacking the SRO7/SOP1-encoded tumor suppressor homologue show increased susceptibility to apoptosis-like cell death on exposure to NaCl stress 总被引:7,自引:0,他引:7
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Yeast cells deleted for the SRO7/SOP1 encoded tumor suppressor homologue show increased sensitivity to NaCl stress. On exposure to growth-inhibiting NaCl concentrations, sro7Delta mutants display a rapid loss in viability that is associated with markers of apoptosis: accumulation of reactive oxygen species, DNA breakage, and nuclear fragmentation. Additional deletion of the yeast metacaspase gene YCA1 prevents the primary fast drop in viability and diminishes nuclear fragmentation and DNA breakage. We also observed that NaCl induced loss in viability of wild-type cells is Yca1p dependent. However, a yeast strain deleted for both SRO7 and its homologue SRO77 exhibits NaCl-induced cell death that is independent on YCA1. Likewise, sro77Delta single mutants do not survive better after additional deletion of the YCA1 gene, and both sro77Delta and sro77Deltayca1Delta mutants display apoptotic characteristics when exposed to growth-inhibiting salinity, suggesting that yeast possesses Yca1p-independent pathway(s) for apoptosis-like cell death. The activity of Yca1p increases with increasing NaCl stress and sro7Delta mutants achieve levels that are higher than in wild-type cells. However, mutants lacking SRO77 do not enhance caspase activity when subject to NaCl stress, suggesting that Sro7p and Sro77p exert opposing effects on the cellular activity of Yca1p. 相似文献
977.
Nine halogenated acetic acids and nine halogenated acrylic acids have been identified in the aqueous extract of Hawaiian Asparagopsis taxiformis. 相似文献
978.
Mannhaupt G Montrone C Haase D Mewes HW Aign V Hoheisel JD Fartmann B Nyakatura G Kempken F Maier J Schulte U 《Nucleic acids research》2003,31(7):1944-1954
The German Neurospora Genome Project has assembled sequences from ordered cosmid and BAC clones of linkage groups II and V of the genome of Neurospora crassa in 13 and 12 contigs, respectively. Including additional sequences located on other linkage groups a total of 12 Mb were subjected to a manual gene extraction and annotation process. The genome comprises a small number of repetitive elements, a low degree of segmental duplications and very few paralogous genes. The analysis of the 3218 identified open reading frames provides a first overview of the protein equipment of a filamentous fungus. Significantly, N.crassa possesses a large variety of metabolic enzymes including a substantial number of enzymes involved in the degradation of complex substrates as well as secondary metabolism. While several of these enzymes are specific for filamentous fungi many are shared exclusively with prokaryotes. 相似文献
979.
p53 stimulates human topoisomerase I activity by modulating its DNA binding 总被引:1,自引:0,他引:1
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The tumor suppressor protein p53 and the human DNA topoisomerase I (htopoI) interact with each other, which leads to a stimulation of the catalytic activity of htopoI. Moreover, p53 stimulates the topoisomerase I-induced recombination repair (TIRR) reaction. However, little was known about how p53 stimulates this topoisomerase I activity. Here we demonstrate that monomeric p53 is sufficient for the stimulation of the topoisomerase I-catalyzed relaxation activity, but the tetrameric form of p53 is required for the stimulation of TIRR. We also show that p53 stimulates topoisomerase I activity by increasing the dissociation of htopoI from DNA. Since htopoI forms a closed ring structure around the DNA, our results suggest that p53 induces a conformational change within htopoI that results in an opening of the clamp, and thereby releases htopoI from DNA. 相似文献
980.
Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells 总被引:35,自引:7,他引:28
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Czauderna F Fechtner M Dames S Aygün H Klippel A Pronk GJ Giese K Kaufmann J 《Nucleic acids research》2003,31(11):2705-2716