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101.
Yoram Nevo Shlomit Aga-Mizrachi Edva Elmakayes Nurit Yanay Keren Ettinger Moran Elbaz Zivia Brunschwig Oshrat Dadush Galit Elad-Sfadia Roni Haklai Yoel Kloog Joab Chapman Shimon Reif 《PloS one》2011,6(3)
The Ras superfamily of guanosine-triphosphate (GTP)-binding proteins regulates a diverse spectrum of intracellular processes involved in inflammation and fibrosis. Farnesythiosalicylic acid (FTS) is a unique and potent Ras inhibitor which decreased inflammation and fibrosis in experimentally induced liver cirrhosis and ameliorated inflammatory processes in systemic lupus erythematosus, neuritis and nephritis animal models. FTS effect on Ras expression and activity, muscle strength and fibrosis was evaluated in the dy2J/dy2J mouse model of merosin deficient congenital muscular dystrophy. The dy2J/dy2J mice had significantly increased RAS expression and activity compared with the wild type mice. FTS treatment significantly decreased RAS expression and activity. In addition, phosphorylation of ERK, a Ras downstream protein, was significantly decreased following FTS treatment in the dy2J/dy2J mice. Clinically, FTS treated mice showed significant improvement in hind limb muscle strength measured by electronic grip strength meter. Significant reduction of fibrosis was demonstrated in the treated group by quantitative Sirius Red staining and lower muscle collagen content. FTS effect was associated with significantly inhibition of both MMP-2 and MMP-9 activities. We conclude that active RAS inhibition by FTS was associated with attenuated fibrosis and improved muscle strength in the dy2J/dy2J mouse model of congenital muscular dystrophy. 相似文献
102.
Ramsgaard L Englert JM Manni ML Milutinovic PS Gefter J Tobolewski J Crum L Coudriet GM Piganelli J Zamora R Vodovotz Y Enghild JJ Oury TD 《PloS one》2011,6(5):e20132
Background
The receptor for advanced glycation end-products (RAGE) has been suggested to modulate lung injury in models of acute pulmonary inflammation. To study this further, model systems utilizing wild type and RAGE knockout (KO) mice were used to determine the role of RAGE signaling in lipopolysaccharide (LPS) and E. coli induced acute pulmonary inflammation. The effect of intraperitoneal (i.p.) and intratracheal (i.t.) administration of mouse soluble RAGE on E. coli injury was also investigated.Methodology/Principal Findings
C57BL/6 wild type and RAGE KO mice received an i.t. instillation of LPS, E. coli, or vehicle control. Some groups also received i.p. or i.t. administration of mouse soluble RAGE. After 24 hours, the role of RAGE expression on inflammation was assessed by comparing responses in wild type and RAGE KO. RAGE protein levels decreased in wild type lung homogenates after treatment with either LPS or bacteria. In addition, soluble RAGE and HMGB1 increased in the BALF after E. coli instillation. RAGE KO mice challenged with LPS had the same degree of inflammation as wild type mice. However, when challenged with E. coli, RAGE KO mice had significantly less inflammation when compared to wild type mice. Most cytokine levels were lower in the BALF of RAGE KO mice compared to wild type mice after E. coli injury, while only monocyte chemotactic protein-1, MCP-1, was lower after LPS challenge. Neither i.p. nor i.t. administration of mouse soluble RAGE attenuated the severity of E. coli injury in wild type mice.Conclusions/Significance
Lack of RAGE in the lung does not protect against LPS induced acute pulmonary inflammation, but attenuates injury following live E. coli challenge. These findings suggest that RAGE mediates responses to E. coli-associated pathogen-associated molecular pattern molecules other than LPS or other bacterial specific signaling responses. Soluble RAGE treatment had no effect on inflammation. 相似文献103.
Sophia S. Barinova Alexey Petrov Eviatar Nevo 《Central European Journal of Biology》2011,6(2):246-259
Comparative analysis of algal communities in the rivers of Israel was completed to highlight the influence of environmental
variables on biodiversity. The study revealed that 671 species of algae and cyanobacteria belonging to nine taxonomic divisions
were present during 2002–2009 in the Yarqon, Alexander, Hadera, Qishon, Oren, Lower and Upper Jordan, and Zin rivers. The
species richness of each river was evaluated by taxonomic structural comparison, geobotanical, hierarchical cluster analysis,
and the degree of relatedness for different levels of taxonomic resolution. The analysis revealed close similarity of the
Upper Jordan and Oren rivers. The average taxonomic distinctness index showed that the Yarqon, Oren, Upper Jordan, and Qishon
communities were partly degraded due to permanent environmental disturbances. The variation in taxonomic distinctness index
showed that the Alexander, Yarqon and Hadera communities were formed not only due to anthropogenic factors but also through
long-term climatic impact. The most abundant indicator species inhabit low streaming and standing alkaline waters of medium
salinity and low to medium organic pollution. The statistical approaches allowed discrimination between climatic and anthropogenic
factors that impact upon the riverine biodiversity in semi-arid environments. Analysis shows the influence of anthropogenic
factors was strongly modulated by climatic impacts causing a marked decease of species richness from north to south. 相似文献
104.
105.
106.
Benoit NE Goldenberg D Deng SX Rosenbaum E Cohen Y Califano JA Shackelford WH Wang XB Sidransky D 《BioTechniques》2005,38(4):635-639
High-throughput genomic mutation screening for primary tumors has characteristically been expensive, labor-intensive, and inadequate to detect low levels of mutation in a background of wild-type signal. We present a new, combined PCR and colorimetric approach that is inexpensive, simple, and can detect the presence of 1% mutation in a background of wild-type. We compared manual dideoxy sequencing of p53 for eight lung cancer samples to a novel assay combining a primer extension step and an enzymatic colorimetric step in a 96-well plate with covalently attached oligonucleotide sequences. For every sample, we were able to detect the presence or absence of the specific mutation with a statistically significant difference between the sample optical density (OD) and the background OD, with a sensitivity and specificity of 100%. This assay is straightforward, accurate, inexpensive, and allows for rapid, high-throughput analysis of samples, making it ideal for genomic mutation or polymorphism screening studies in both clinical and research settings. 相似文献
107.
Among carbon sources studied, cellobiose and mannitol provided the highest laccase (Lac) activity (648 and 742 U1-1, respectively) of Trametes versicolor 775 while glucose gave maximum manganese peroxidase (MnP) and peroxidase activities (44 and 114U1-1, respectively). Citrus fruit peel as growth substrate enhanced Lac activity 7-fold when compared to the medium with cellobiose, whereas grape vine sawdust increased MnP and peroxidase activity up to 148 and 677U1-1, respectively. 相似文献
108.
Shams I Avivi A Nevo E 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2005,142(3):376-382
The composition of oxygen (O2), carbon dioxide (CO2), and soil humidity in the underground burrows from three species of the Israeli subterranean mole rat Spalax ehrenbergi superspecies were studied in their natural habitat. Two geographically close populations of each species from contrasting soil types were probed. Maximal CO2 levels (6.1%) and minimal O2 levels (7.2%) were recorded in northern Israel in the breeding mounds of S. carmeli in a flooded, poor drained field of heavy clay soil with very high volumetric water content. The patterns of gas fluctuations during the measurement period among the different Spalax species studied were similar. The more significant differentiation in gas levels was not among species, but between neighboring populations inhabiting heavy soils or light soils: O2 was lower and CO2 was higher in the heavy soils (clay and basaltic) compared to the relatively light soils (terra rossa and rendzina). The extreme values of gas concentration, which occurred during the rainy season, seemed to fluctuate with partial flooding of the tunnels, animal digging activity, and over-crowded breeding mounds inhabited by a nursing female and her offspring. The gas composition and soil water content in neighboring sites with different soil types indicated large differences in the levels of hypoxic-hypercapnic stress in different populations of the same species. A growing number of genes associated with hypoxic stress have been shown to exhibit structural and functional differences between the subterranean Spalax and the above-ground rat (Rattus norvegicus), probably reflecting the molecular adaptations that Spalax went through during 40 million years of evolution to survive efficiently in the severe fluctuations in gas composition in the underground habitat. 相似文献
109.
The energy landscape of proteins is thought to have an intricate, corrugated structure. Such roughness should have important consequences on the folding and binding kinetics of proteins, as well as on their equilibrium fluctuations. So far, no direct measurement of protein energy landscape roughness has been made. Here, we combined a recent theory with single-molecule dynamic force spectroscopy experiments to extract the overall energy scale of roughness epsilon for a complex consisting of the small GTPase Ran and the nuclear transport receptor importin-beta. The results gave epsilon > 5k(B)T, indicating a bumpy energy surface, which is consistent with the ability of importin-beta to accommodate multiple conformations and to interact with different, structurally distinct ligands. 相似文献
110.
We have shown previously that responses to lysophosphatidic acid (LPA) in Xenopus oocytes exhibit pronounced rapid homologous desensitization mediated by Go family of G-proteins (Itzhaki-Van Ham et al., 2004, J Cell Physiol, 200: 125-133). The present study was aimed at examining the involvement of Go G-proteins in rapid heterologous desensitization of native and expressed G-protein-coupled receptors in Xenopus oocytes. Threshold stimulation of the native lysophosphatidic acid receptors (LPA-Rs) induced about 50% rapid desensitization of responses evoked by stimulation of either native trypsin or expressed M1-muscarinic cholinergic receptors (M1-Rs). Similarly, threshold stimulation of expressed M1-Rs or thyrotropin-releasing hormone receptors induced 40% rapid desensitization of responses to LPA. Inactivation of all Gi/o G-proteins with pertussis toxin (PTX) completely abolished rapid heterologous desensitization in all protocols. Depletion of either Galphao or Galphao1 by antisense oligodeoxynucleotides targeted at either member of the Galphao family decreased or completely abolished rapid heterologous desensitization. Expression of two dominant negative mutants of the human Galphao family, highly homologous to oocyte Galphao species, either decreased or virtually abolished rapid desensitization. Homologous and heterologous desensitizations of the LPA response were non-additive and proceeded, apparently, via the same pathway. We conclude that Go G-proteins mediate both homologous and heterologous rapid desensitization of responses mediated by G-protein-coupled receptors (GPCRs) coupled to the phosphoinositide phospholipase C-inositol 1,4,5-trisphosphate-Ca(2+) (PI-PLC-InsP(3)-Ca(2+)) pathway in Xenopus oocytes. 相似文献