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721.
Alan M. Eckler Caroline Wilder Antonio Castanon Veronica M. Ferris Rachael A. Lamere Benjamin A. Perrin Ross Pearlman Blaise White Clifton Byrd Nicholas Ludvik Nona Nichols Kristen Poole-Sumrall Elizabeth Sztul Melanie L. Styers 《PloS one》2013,8(2)
Membrane trafficking is essential to eukaryotic life and is controlled by a complex network of proteins that regulate movement of proteins and lipids between organelles. The GBF1/GEA family of Guanine nucleotide Exchange Factors (GEFs) regulates trafficking between the endoplasmic reticulum and Golgi by catalyzing the exchange of GDP for GTP on ADP Ribosylation Factors (Arfs). Activated Arfs recruit coat protein complex 1 (COP-I) to form vesicles that ferry cargo between these organelles. To further explore the function of the GBF1/GEA family, we have characterized a fission yeast mutant lacking one copy of the essential gene gea1 (gea1+/−), the Schizosaccharomyces pombe ortholog of GBF1. The haploinsufficient gea1+/− strain was shown to be sensitive to the GBF1 inhibitor brefeldin A (BFA) and was rescued from BFA sensitivity by gea1p overexpression. No overt defects in localization of arf1p or arf6p were observed in gea1+/− cells, but the fission yeast homolog of the COP-I cargo sac1 was mislocalized, consistent with impaired COP-I trafficking. Although Golgi morphology appeared normal, a slight increase in vacuolar size was observed in the gea1+/− mutant strain. Importantly, gea1+/− cells exhibited dramatic cytokinesis-related defects, including disorganized contractile rings, an increased septation index, and alterations in septum morphology. Septation defects appear to result from altered secretion of enzymes required for septum dynamics, as decreased secretion of eng1p, a β-glucanase required for septum breakdown, was observed in gea1+/− cells, and overexpression of eng1p suppressed the increased septation phenotype. These observations implicate gea1 in regulation of septum breakdown and establish S. pombe as a model system to explore GBF1/GEA function in cytokinesis. 相似文献
722.
Christopher Uhlig Pedro L Silva Débora Ornellas Raquel S Santos Paulo J Miranda Peter M Spieth Thomas Kiss Michael Kasper B?rbel Wiedemann Thea Koch Marcelo M Morales Paolo Pelosi Marcelo Gama de Abreu Patricia RM Rocco 《Respiratory research》2014,15(1):56
Introduction
We investigated the effects of intravenous and intratracheal administration of salbutamol on lung morphology and function, expression of ion channels, aquaporin, and markers of inflammation, apoptosis, and alveolar epithelial/endothelial cell damage in experimental pulmonary (p) and extrapulmonary (exp) mild acute respiratory distress syndrome (ARDS).Methods
In this prospective randomized controlled experimental study, 56 male Wistar rats were randomly assigned to mild ARDS induced by either intratracheal (n = 28, ARDSp) or intraperitoneal (n = 28, ARDSexp) administration of E. coli lipopolysaccharide. Four animals with no lung injury served as controls (NI). After 24 hours, animals were anesthetized, mechanically ventilated in pressure-controlled mode with low tidal volume (6 mL/kg), and randomly assigned to receive salbutamol (SALB) or saline 0.9% (CTRL), intravenously (i.v., 10 μg/kg/h) or intratracheally (bolus, 25 μg). Salbutamol doses were targeted at an increase of ≈ 20% in heart rate. Hemodynamics, lung mechanics, and arterial blood gases were measured before and after (at 30 and 60 min) salbutamol administration. At the end of the experiment, lungs were extracted for analysis of lung histology and molecular biology analysis. Values are expressed as mean ± standard deviation, and fold changes relative to NI, CTRL vs. SALB.Results
The gene expression of ion channels and aquaporin was increased in mild ARDSp, but not ARDSexp. In ARDSp, intravenous salbutamol resulted in higher gene expression of alveolar epithelial sodium channel (0.20 ± 0.07 vs. 0.68 ± 0.24, p < 0.001), aquaporin-1 (0.44 ± 0.09 vs. 0.96 ± 0.12, p < 0.001) aquaporin-3 (0.31 ± 0.12 vs. 0.93 ± 0.20, p < 0.001), and Na-K-ATPase-α (0.39 ± 0.08 vs. 0.92 ± 0.12, p < 0.001), whereas intratracheal salbutamol increased the gene expression of aquaporin-1 (0.46 ± 0.11 vs. 0.92 ± 0.06, p < 0.001) and Na-K-ATPase-α (0.32 ± 0.07 vs. 0.58 ± 0.15, p < 0.001). In ARDSexp, the gene expression of ion channels and aquaporin was not influenced by salbutamol. Morphological and functional variables and edema formation were not affected by salbutamol in any of the ARDS groups, regardless of the route of administration.Conclusion
Salbutamol administration increased the expression of alveolar epithelial ion channels and aquaporin in mild ARDSp, but not ARDSexp, with no effects on lung morphology and function or edema formation. These results may contribute to explain the negative effects of β2-agonists on clinical outcome in ARDS. 相似文献723.
Tatiana Selchenkova Clément Fran?ois Daniele Sch?n Alexandra Corneyllie Fabien Perrin Barbara Tillmann 《PloS one》2014,9(11)
The present study investigated whether a temporal hierarchical structure favors implicit learning. An artificial pitch grammar implemented with a set of tones was presented in two different temporal contexts, notably with either a strongly metrical structure or an isochronous structure. According to the Dynamic Attending Theory, external temporal regularities can entrain internal oscillators that guide attention over time, allowing for temporal expectations that influence perception of future events. Based on this framework, it was hypothesized that the metrical structure provides a benefit for artificial grammar learning in comparison to an isochronous presentation. Our study combined behavioral and event-related potential measurements. Behavioral results demonstrated similar learning in both participant groups. By contrast, analyses of event-related potentials showed a larger P300 component and an earlier N2 component for the strongly metrical group during the exposure phase and the test phase, respectively. These findings suggests that the temporal expectations in the strongly metrical condition helped listeners to better process the pitch dimension, leading to improved learning of the artificial grammar. 相似文献
724.
725.
726.
Denden S Khelil AH Knani J Lakhdar R Perrin P Lefranc G Chibani JB 《Genetics and molecular biology》2010,33(1):23-26
Alpha-1-antitrypsin (AAT) plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD). In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val), PiM2 (Arg101His), PiM3 (Glu376Asp), PiS (Glu264Val) and PiZ (Glu342Lys) SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3) and the emphysematous type of COPD. In addition, FEV(1) annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms. 相似文献
727.
728.
Lavery GG Walker EA Draper N Jeyasuria P Marcos J Shackleton CH Parker KL White PC Stewart PM 《The Journal of biological chemistry》2006,281(10):6546-6551
The local generation of active glucocorticoid by NADPH-dependent, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) oxoreductase activity, has emerged as an important factor in regulating hepatic glucose output and visceral adiposity. We have proposed that this NADPH is generated within the endoplasmic reticulum by the enzyme hexose-6-phosphate dehydrogenase. To address this hypothesis, we generated mice with a targeted inactivation of the H6PD gene. These mice were unable to convert 11-dehydrocorticosterone (11-DHC) to corticosterone but demonstrated increased corticosterone to 11-DHC conversion consistent with lack of 11beta-HSD1 oxoreductase and a concomitant increase in dehydrogenase activity. This increased corticosterone clearance in the knock-out mice resulted in a reduction in circulating corticosterone levels. Our studies define the critical requirement of hexose-6-phosphate dehydrogenase for 11beta-HSD1 oxoreductase activity and add a new dimension to the investigation of 11beta-HSD1 as a therapeutic target in patients with the metabolic syndrome. 相似文献
729.
A bipartite system for the constitutive and inducible expression of high levels of foreign proteins in plants 总被引:3,自引:1,他引:2
Cañizares MC Liu L Perrin Y Tsakiris E Lomonossoff GP 《Plant biotechnology journal》2006,4(2):183-193
We have developed combined transgene/virus vector systems for the expression of heterologous proteins in plants. The systems are based on the bipartite RNA plant virus, cowpea mosaic virus (CPMV), and involve the amplification of integrated copies of either full-length or deleted versions of RNA-2 carrying a foreign gene. In the case of plants transgenic for full-length versions of RNA-2 carrying the green fluorescent protein (GFP), amplification can be achieved by supplying RNA-1 either exogenously or by crossing. This allows either inducible or constitutive expression of the foreign gene and results in an infection that can be passaged to further plants. Replication of deleted versions of RNA-2 harbouring GFP requires the presence of both RNA-1 and a suppressor of gene silencing, a function which we show can be supplied by HcPro from potato virus Y. Replication of the deleted versions of RNA-2 can be achieved by supplying the suppressor and RNA-1 either exogenously or by crossing, showing that this system can also be used in an inducible and constitutive format. The use of deleted forms of RNA-2 has the advantage that no infectious virus is produced, providing an effective method of biocontainment. The CPMV-based systems have advantages over existing plant expression systems in terms of the expression levels obtainable and the simplicity and flexibility of use, and should be of great practical benefit in the development of plants as bioreactors. 相似文献
730.
Jacqueline Fournier-Caruana Bertrand Poirier Geneviève Haond Corinne Jallet Florence Fuchs No?l Tordo Pierre Perrin 《Biologicals》2003,31(1):9-16
Quality control of human rabies vaccines performed by National Control Laboratories (NCLs) prior to marketing vaccines batches requires in vivo and in vitro potency assays as requested by the relevant European Pharmacopoeia monographs, OMCLs guidelines and WHO technical recommendations.The aim of the present study was to check the suitability of an enzyme-linked immunosorbent assay (ELISA) using a virus neutralizing monoclonal antibody, directed to the rabies virus glycoprotein, to monitor the consistency of the lot to lot rabies vaccines production. Furthermore, this work was implemented to establish in house specifications for the glycoprotein content. 相似文献