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961.
962.
963.
Clarke MB Wright R Irwin D Bose S Van Rheen Z Birari R Stenmark KR McCord JM Nozik-Grayck E 《Free radical biology & medicine》2010,49(12):2032-2039
Delivery of recombinant superoxide dismutase to the lung is limited by its short half-life and poor tissue penetration. We hypothesized that a chimeric protein, SOD2/3, containing the enzymatic domain of manganese superoxide dismutase (SOD2) and the heparan-binding domain of extracellular superoxide dismutase (SOD3), would allow for the delivery of more sustained lung and pulmonary vascular antioxidant activity compared to SOD2. We administered SOD2/3 to rats by intratracheal (i.t.), intraperitoneal (i.p.), or intravenous (i.v.) routes and evaluated the presence, localization, and activity of lung SOD2/3 1 day later using Western blot, immunohistochemistry, and SOD activity gels. The effect of i.t. SOD2/3 on the pulmonary and systemic circulation was studied in vivo in chronically catheterized rats exposed to acute hypoxia. Active SOD2/3 was detected in lung 1 day after i.t. administration but not detected after i.p. or i.v. SOD2/3 administration or i.t. SOD2. The physiologic response to acute hypoxia, vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation, was enhanced in rats treated 1 day earlier with i.t. SOD2/3. These findings indicate that i.t. administration of SOD2/3 effectively delivers sustained enzyme activity to the lung as well as pulmonary circulation and has a longer tissue half-life compared to native SOD2. Further testing in models of chronic lung or pulmonary vascular diseases mediated by excess superoxide should consider the longer tissue half-life of SOD2/3 as well as its potential systemic vascular effects. 相似文献
964.
Andrea Staršíchová Eva Lincová Zuzana Pernicová Alois Kozubík Karel Souček 《Cellular signalling》2010,22(11):1734-1744
Chronic inflammation plays an important role in the initiation and progression of various human diseases including benign prostatic hyperplasia or prostate cancer. Here we show that the proinflammatory cytokine interleukin-6 (IL-6) has prosurvival effects and chronically activates the Jak2/STAT3 signalling pathway in a model of benign prostatic hyperplasia (BPH-1). We demonstrate that the antiinflammatory cytokine transforming growth factor-β1 (TGF-β1), which also permanently activates its canonical signalling pathway through SMAD proteins in BPH-1 cells, modifies the effects of IL-6 on cell proliferation. Importantly, TGF-β1 inhibits IL-6 signal transduction by decreasing the phosphorylation levels of STAT3. This effect is associated with decreased expression of Jak2 at both mRNA and protein levels. Moreover, we showed that TGF-β1 inhibits IL-6-induced expression of the cancer-associated gene MUC1. These observations demonstrated a novel interaction between TGF-β1 and IL-6 signalling and suggested another mechanism of how defects in TGF-β signalling, frequently associated with prostate pathologies, can contribute to the disruption of tissue homeostasis. 相似文献
965.
Peter Vďačný Eva Tirjaková Tímea Tóthová Peter Pristaš Peter Javorský 《European journal of protistology》2010,46(4):319-333
The morphology, ontogenesis, encystment, and 18S rRNA gene sequence of a new soil hypotrich ciliate, Kahliella matisi, were studied. Main characteristics of K. matisi are: (1) two short and six longitudinal cirral rows right of the adoral zone of membranelles and four longitudinal rows left of it; (2) three dorsal kineties, of which kinety 1 extends along the left cell margin, kinety 2 runs in a slightly sigmoidal line, and kinety 3 is distinctly shortened posteriorly. Ontogenesis is similar to that in congeners, especially in the development of the marginal rows and long dorsal kineties, the preservation of some old cirral rows after division, and the direction of the neokinetal wave. However, there are some peculiarities: (1) reorganization of the proximal parental adoral membranelles; (2) splitting of opisthe's anlage II into the cirral streak II and III; and (3) formation of the parental cirral row R3 from anlagen IV and V. During encystment, the body diminishes and becomes globular, the nuclear apparatus is reorganized, and the ciliature is resorbed. In our molecular phylogenies, the family Kahliellidae is polyphyletic and the position of K. matisi is rather poorly resolved, indicating a relationship with oxytrichids. 相似文献
966.
Eva Stauffer Alexander Westermann Gabriele Wagner Andreas Wachter 《The Plant journal : for cell and molecular biology》2010,64(2):243-255
Alternative splicing (AS) of precursor mRNAs is a widespread phenomenon in plants; however, many questions, especially regarding its regulation and functional implications, remain to be elucidated. In vertebrates, polypyrimidine tract‐binding proteins (PTBs) have been identified as key splicing factors influencing splice site selection and orchestrating coordinated splicing programmes during developmental processes. Here, we analysed three PTB homologues from Arabidopsis thaliana and provide evidence for their gene regulatory potential based on AS and a splicing‐independent mechanism. Our data reveal that Arabidopsis PTB homologues are subject to extensive auto‐ and cross‐regulation via AS‐coupled nonsense‐mediated decay, thereby establishing a basis for interlinking their expression. Furthermore, the multiple modes of action of Arabidopsis PTB homologues are reflected in their subcellular localization in the nucleus, cytosol and processing bodies. This work provides insight into the regulation of AS in plants and highlights the regulatory potential of the multifunctional plant PTB homologues, which might have important implications in diverse biological processes. 相似文献
967.
Schiller R Tichotová L Pavlík J Buchta V Melichar B Votruba I Kunes J Spulák M Pour M 《Bioorganic & medicinal chemistry letters》2010,20(24):7358-7360
A series of 3-aryl-5-acyloxymethyl-5,6-dihydro-2H-pyran-2-ones, related to highly antifungally active butenolides, was synthesized via cyclization of substituted δ-hydroxy acids as the key step, and evaluated for their in vitro antifungal activity and cytostatic activity. While the extension of the furanone ring to pyranone led to a complete loss of the antifungal effect, some of the compounds displayed promising effect against several cell lines, including the resistant colorectal carcinoma cells. 相似文献
968.
Tricyclic dihydroquinazolinones as novel 5-HT2C selective and orally efficacious anti-obesity agents
Saleem Ahmad Khehyong Ngu Keith J. Miller Ginger Wu Chen-pin Hung Sarah Malmstrom Ge Zhang Eva O’Tanyi William J. Keim Mary Jane Cullen Kenneth W. Rohrbach Michael Thomas Thao Ung Qinling Qu Jinping Gan Rangaraj Narayanan Mary Ann Pelleymounter Jeffrey A. Robl 《Bioorganic & medicinal chemistry letters》2010,20(3):1128-1133
Agonists of the 5-HT2C receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT2B receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT2C agonists with no detectable agonism of the 5-HT2B receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing. 相似文献
969.
Javier García‐Nafría Gabriela Ondrovičová Elena Blagova Vladimir M. Levdikov Jacob A. Bauer Carolyn K. Suzuki Eva Kutejová Anthony J. Wilkinson Keith S. Wilson 《Protein science : a publication of the Protein Society》2010,19(5):987-999
ATP‐dependent proteases are crucial for cellular homeostasis. By degrading short‐lived regulatory proteins, they play an important role in the control of many cellular pathways and, through the degradation of abnormally misfolded proteins, protect the cell from a buildup of aggregates. Disruption or disregulation of mammalian mitochondrial Lon protease leads to severe changes in the cell, linked with carcinogenesis, apoptosis, and necrosis. Here we present the structure of the proteolytic domain of human mitochondrial Lon at 2 Å resolution. The fold resembles those of the three previously determined Lon proteolytic domains from Escherichia coli, Methanococcus jannaschii, and Archaeoglobus fulgidus. There are six protomers in the asymmetric unit, four arranged as two dimers. The intersubunit interactions within the two dimers are similar to those between adjacent subunits of the hexameric ring of E. coli Lon, suggesting that the human Lon proteolytic domain also forms hexamers. The active site contains a 310 helix attached to the N‐terminal end of α‐helix 2, which leads to the insertion of Asp852 into the active site, as seen in M. jannaschii. Structural considerations make it likely that this conformation is proteolytically inactive. When comparing the intersubunit interactions of human with those of E. coli Lon taken with biochemical data leads us to propose a mechanism relating the formation of Lon oligomers with a conformational shift in the active site region coupled to a movement of a loop in the oligomer interface, converting the proteolytically inactive form seen here to the active one in the E. coli hexamer. 相似文献
970.
Ad N Cheng DC Martin J Berglin EE Chang BC Doukas G Gammie JS Nitta T Wolf RK Puskas JD 《Innovations (Philadelphia, Pa.)》2010,5(2):74-83
OBJECTIVE:: This purpose of this consensus conference was to determine whether surgical atrial fibrillation (AF) ablation during cardiac surgery improves clinical and resource outcomes compared with cardiac surgery alone in adults undergoing cardiac surgery for valve or coronary artery bypass grafting. METHODS:: Before the consensus conference, the consensus panel reviewed the best available evidence, whereby systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of validity and importance. Evidence-based statements were created, and consensus processes were used to determine the ensuing recommendations. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of recommendation. RESULTS:: The consensus panel agreed on the following statements in patients with AF undergoing cardiac surgery concomitant surgical ablation: CONCLUSIONS:: Given these evidence-based statements, the consensus panel stated that, in patients with persistent and permanent AF undergoing cardiac surgery, concomitant surgical ablation is recommended to increase incidence of sinus rhythm at short- and long-term follow-up (class 1, level A); to reduce the risk of stroke and thromboembolic events (class 2a, level B); to improve EF (class 2a, level A); and to exercise tolerance (class 2a, level A) and long-term survival (class 2a, level B). 相似文献