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1
el-Mansi, E. M. T., C. MacKintosh, K. Duncan, W. H. Holms, and H. G. Nimmo. "Molecular cloning and over-expression of the glyoxylate bypass operon from Escherichia coli ML308." Biochemical Journal 242, no. 3 (March 15, 1987): 661–65. http://dx.doi.org/10.1042/bj2420661.
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A recombinant plasmid carrying an 11 kb restriction-endonuclease-ClaI fragment of genomic DNA from Escherichia coli ML308 was constructed. This plasmid complements an aceA mutation. The plasmid encodes the structural genes of the glyoxylate bypass operon, namely malate synthase A (aceB), isocitrate lyase (aceA) and isocitrate dehydrogenase kinase/phosphatase (aceK), as judged by overexpression of enzyme activities and transcription/translation experiments in vitro. Subcloning confirmed that expression of the aceK gene is essential for growth on acetate.
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Monazzam, Shafagh, Karly Ann Williams, Trevor J. Shelton, Arash Calafi, and Brian M. Haus. "Anterior centre-edge angle on sagittal CT: a comparison of normal hips to dysplastic hips." HIP International 28, no. 5 (May 17, 2018): 535–41. http://dx.doi.org/10.1177/1120700017752569.
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Purpose: The anterior centre-edge angle (ACEA) describes anterior acetabular coverage on false profile radiographs. Variability associated with pelvic tilt, radiographic projection, and identifying the true anterior edge, causes discrepancies in measuring an accurate ACEA. Computed tomography (CT) has the potential of improving the accuracy of ACEA. However, because the ACEA on sagittal CT has been shown to not be equivalent to ACEA on false profile radiographs, the normal range of ACEA on CT currently remains unknown and cannot reliably be used to determine over/under coverage. We therefore asked: what is the normal variation of ACEA corrected for pelvic tilt on sagittal CT and how does this compare to dysplastic hips? Material and Methods: A retrospective review was conducted on patients 10–35 who underwent CT for non-orthopedic related issues and patients with known hip dysplasia. The ACEA was measured on a sagittal slice corresponding to the centre of the femoral head on the axial slice and adjusted for pelvic tilt. A statistical comparison was then performed. Results: A total of 320 normal patients and 22 patients with hip dysplasia were reviewed. The mean ACEA for all ages was 50° ± 8°, (range: 23–81º), with a larger mean ACEA for males (51°) than females (49°). The ACEA mean for dysplastic hips was 30° ± 11° with a statistically significant difference in mean from the normal hip group ( p < 0.0001). Conclusion: The ACEA can be reliably measured on sagittal CT and significantly differs from dysplastic hips. ACEA measurements above 66° or below 34° may represent anterior over and under coverage.
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Ramírez-Trujillo, J. A., S. Encarnación, E. Salazar, A. García de los Santos, M. F. Dunn, D. W. Emerich, E. Calva, and I. Hernández-Lucas. "Functional Characterization of the Sinorhizobium meliloti Acetate Metabolism Genes aceA, SMc00767, and glcB." Journal of Bacteriology 189, no. 16 (May 25, 2007): 5875–84. http://dx.doi.org/10.1128/jb.00385-07.
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ABSTRACT The genes encoding malate synthase (glcB) and isocitrate lyase (aceA) and a 240-bp open reading frame (SMc00767) located downstream of aceA were isolated and functionally characterized in Sinorhizobium meliloti. Independent and double interposon mutants of each gene were constructed, and the corresponding phenotypes were analyzed. aceA mutants failed to grow on acetate, and mutants deficient in SMc00767 were also affected in acetate utilization. In contrast, mutants deficient in glcB grew on acetate similar to wild-type strain Rm5000. Complementation experiments showed that aceA and SMc00767 gene constructs were able to restore the growth on acetate in the corresponding single mutants. aceA-glcB, aceA-SMc00767, and glcB-SMc00767 double knockouts were also unable to grow on acetate, but this ability was recovered when the wild-type aceA-glcB or aceA-SMc00767 loci were introduced into the double mutants. These data confirm the functional role of aceA and SMc00767 and show that glcB, in the absence of SMc00767, is required for acetate metabolism. Isocitrate lyase and malate synthase activities were measured in strain Rm5000, the mutant derivatives, and complemented strains. aceA and glcB were able to complement the enzymatic activity lacking in the corresponding single mutants. The enzymatic activities also showed that SMc00767 represses the activity of isocitrate lyase in cells grown on acetate. Gene fusions confirmed the repressor role of SMc00767, which regulates aceA expression at the transcriptional level. Comparison of the transcriptional profiles of the SMc00767 mutant and wild-type strain Rm5000 showed that SMc00767 represses the expression of a moderate number of open reading frames, including aceA; thus, we propose that SMc00767 is a novel repressor involved in acetate metabolism in S. meliloti. Genetic and functional analyses indicated that aceA and SMc00767 constitute a functional two-gene operon, which is conserved in other α-proteobacteria. Alfalfa plants infected with the aceA and glcB mutants were not impaired in nodulation or nitrogen fixation, and so the glyoxylate cycle is not required in the Rhizobium-legume symbiosis.
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Zapała, Łukasz, Grzegorz Niemczyk, Piotr Zapała, Artur Wdowiak, Iwona Bojar, Tomasz Kluz, Aleksandra Szopa, Anna Serefko, Piotr Radziszewski, and Andrzej Wróbel. "The Cannabinoid Ligand Arachidonyl-2′-Chloroethylamide (ACEA) Ameliorates Depressive and Overactive Bladder Symptoms in a Corticosterone-Induced Female Wistar Rat Model." International Journal of Molecular Sciences 24, no. 4 (February 14, 2023): 3820. http://dx.doi.org/10.3390/ijms24043820.
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There is growing need to increase the knowledge on the cannabinoid ligands in the treatment of overactive bladder. Among potential candidates, arachidonyl-2′-chloroethylamide (ACEA), a selective cannabinoid CB1 receptor agonist is proposed. The aim of this paper was to determine if ACEA, a selective cannabinoid CB1 receptor agonist, could reverse the effects of corticosterone (CORT), characteristic of depressive and bladder overactivity potential. The animals (48 female rats) were divided into four groups: I—control, II—received CORT, III—received ACEA, and IV—received the combination of CORT and ACEA. The conscious cystometry, forced swim test (FST), and locomotor activity measurements were performed 3 days after the last dose of ACEA, followed by ELISA measurements. In group IV, ACEA restored urodynamic parameters that were altered by CORT. CORT prolonged the immobility time in FST and the values were lowered by ACEA. ACEA normalized the expression of c-Fos in all the analyzed central micturition centers (group IV vs. group II). ACEA restored the CORT-induced changes in the biomarkers in urine (BDNF, NGF), bladder detrusor (VAChT, Rho kinase), bladder urothelium (CGRP, ATP, CRF, OCT-3, TRPV1), and hippocampus (TNF-, IL-1β and Il-6, CRF, IL-10, BDNF, NGF). In conclusion, ACEA was proven to reverse CORT-induced changes in both cystometric and biochemical parameters that are determinants of OAB/depression, which represents an example of an existing link between OAB and depression via cannabinoid receptors.
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McFarlane, Claude, David S. Warner, Antoun Nader, and Franklin Dexter. "Glycine Receptor Antagonism." Anesthesiology 82, no. 4 (April 1, 1995): 963–68. http://dx.doi.org/10.1097/00000542-199504000-00020.
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Background Glycine and glutamate binding sites are allosterically coupled at the N-methyl-D-aspartate (NMDA) receptor complex. Previous studies have shown that antagonism of glutamate at the NMDA receptor reduces the minimum alveolar concentration (MAC) for volatile anesthetics. 5-Nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA-1021) is a competitive antagonist at the glycine recognition site of the NMDA receptor. The purpose of this study was to determine whether glycine receptor antagonism also reduces volatile anesthetic requirements in the rat. Methods In experiment 1, Sprague-Dawley rats were anesthetized with halothane in 50% O2-balance N2 and their lungs mechanically ventilated. They were randomly assigned to one of three groups according to the dose of ACEA-1021 administered (0, 20, or 40 mg/kg intravenously; n = 6). The bolus dose of ACEA-1021 was followed by a continuous intravenous infusion of vehicle or ACEA-1021 at 14 mg.kg-1.h-1. Halothane MAC was then determined by the tail-clamp method. In experiment 2, awake rats were randomly assigned to groups according to the same dosages of ACEA-1021 as in experiment 1. Arterial CO2 tension and mean arterial pressure were recorded before and 5 and 30 min after the start of the infusion. The infusion was then stopped, and the time to recovery of the righting reflex was recorded. Results In experiment 1, ACEA-1021 decreased halothane MAC (mean +/- SD) in a dose-dependent manner (control, 0.95 +/- 0.15 vol%; ACEA-1021 20 mg/kg, 0.50 +/- 0.14 vol%; ACEA-1021 40 mg/kg, 0.14 +/- 0.16 vol%; P < 0.01). In experiment 2, arterial CO2 tension was increased by ACEA-1021 (control, 38 +/- 3 mmHg; ACEA-1021 20 mg/kg, 43 +/- 3 mmHg; ACEA-1021 40 mg/kg, 48 +/- 2 mmHg; P < 0.01). Mean arterial pressure was not affected by any dose of ACEA-1021. The righting reflex was abolished in rats receiving ACEA-1021 40 mg/kg only and recovered 30 +/- 7 min after discontinuation of the infusion. Conclusions Halothane MAC reduction by glycine receptor antagonism was greater than that previously observed for antagonism of glutamate at the NMDA or AMPA receptor. In rats receiving ACEA-1021 only, minimal hemodynamic depression and moderate hypoventilation were observed. Antagonism of glycine at the NMDA receptor recognition site offers a potential mechanism of action of anesthesia.
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Gerstmeir, Robert, Annette Cramer, Petra Dangel, Steffen Schaffer, and Bernhard J. Eikmanns. "RamB, a Novel Transcriptional Regulator of Genes Involved in Acetate Metabolism of Corynebacterium glutamicum." Journal of Bacteriology 186, no. 9 (May 1, 2004): 2798–809. http://dx.doi.org/10.1128/jb.186.9.2798-2809.2004.
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ABSTRACT The adaptation of Corynebacterium glutamicum to acetate as a carbon and energy source involves transcriptional regulation of the pta-ack operon coding for the acetate-activating enzymes phosphotransacetylase and acetate kinase and of the aceA and aceB genes coding for the glyoxylate cycle enzymes isocitrate lyase and malate synthase, respectively. Deletion and mutation analysis of the respective promoter regions led to the identification of highly conserved 13-bp motifs (AA/GAACTTTGCAAA) as cis-regulatory elements for expression of the pta-ack operon and the aceA and aceB genes. By use of DNA affinity chromatography, a 53-kDa protein specifically binding to the promoter/operator region of the pta-ack operon was purified. Mass spectrometry and peptide mass fingerprinting identified the protein as a putative transcriptional regulator (which was designated RamB). Purified His-tagged RamB protein was shown to bind specifically to both the pta-ack and the aceA/aceB promoter/operator regions. Directed deletion of the ramB gene in the genome of C. glutamicum resulted in mutant strain RG1. Whereas the wild type of C. glutamicum showed high-level specific activities of acetate kinase, phosphotransacetylase, isocitrate lyase, and malate synthase when grown on acetate and low-level specific activities when grown on glucose as sole carbon and energy sources, mutant RG1 showed high-level specific activities with all four enzymes irrespective of the substrate. Comparative transcriptional cat fusion experiments revealed that this deregulation takes place at the level of transcription. The results indicate that RamB is a negative transcriptional regulator of genes involved in acetate metabolism of C. glutamicum.
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Liu, Binbing, Yang Tian, Yuchen Li, Pei Wu, Yongzhi Zhang, Jiaolin Zheng, and Huaizhang Shi. "ACEA Attenuates Oxidative Stress by Promoting Mitophagy via CB1R/Nrf1/PINK1 Pathway after Subarachnoid Hemorrhage in Rats." Oxidative Medicine and Cellular Longevity 2022 (February 24, 2022): 1–18. http://dx.doi.org/10.1155/2022/1024279.
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Background and Purpose. Oxidative stress plays a pivotal role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). The CB1R agonist ACEA has been reported to have a neuroprotective effect in many central nervous system diseases. Our study was aimed at exploring the effect and mechanism of ACEA in an experimental SAH model. Method. Endovascular perforation was performed to establish a SAH model of rats. ACEA was administered intraperitoneally 1 h after SAH. The CB1R antagonist AM251 was injected intraperitoneally 1 h before SAH induction. Adenoassociated virus- (AAV-) Nrf1 shRNA was infused into the lateral ventricle 3 weeks before SAH induction. Neurological tests, immunofluorescence, DHE, TUNEL, Nissl staining, transmission electron microscopy (TEM), and Western blot were performed. Results. The expression of CB1R, Nrf1, PINK1, Parkin, and LC3II increased and peaked at 24 h after SAH. ACEA treatment exhibited the antioxidative stress and antiapoptosis effects after SAH. In addition, ACEA treatment increased the expression of Nrf1, PINK1, Parkin, LC3II, and Bcl-xl but repressed the expression of Romo-1, Bax, and cleaved caspase-3. Moreover, the TEM results demonstrated that ACEA promoted the formation of mitophagosome and maintained the normal mitochondrial morphology of neurons. The protective effect of ACEA was reversed by AM251 and Nrf1 shRNA, respectively. Conclusions. This study demonstrated that ACEA alleviated oxidative stress and neurological dysfunction by promoting mitophagy after SAH, at least in part via the CB1R/Nrf1/PINK1 signaling pathway.
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Cramer, Annette, Robert Gerstmeir, Steffen Schaffer, Michael Bott, and Bernhard J. Eikmanns. "Identification of RamA, a Novel LuxR-Type Transcriptional Regulator of Genes Involved in Acetate Metabolism of Corynebacterium glutamicum." Journal of Bacteriology 188, no. 7 (April 1, 2006): 2554–67. http://dx.doi.org/10.1128/jb.188.7.2554-2567.2006.
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ABSTRACT In Corynebacterium glutamicum, the acetate-activating enzymes phosphotransacetylase and acetate kinase and the glyoxylate cycle enzymes isocitrate lyase and malate synthase are coordinately up-regulated in the presence of acetate in the growth medium. This regulation is due to transcriptional control of the respective pta-ack operon and the aceA and aceB genes, brought about at least partly by the action of the negative transcriptional regulator RamB. Using cell extracts of C. glutamicum and employing DNA affinity chromatography, mass spectrometry, and peptide mass fingerprinting, we identified a LuxR-type transcriptional regulator, designated RamA, which binds to the pta-ack and aceA/aceB promoter regions. Inactivation of the ramA gene in the genome of C. glutamicum resulted in mutant RG2. This mutant was unable to grow on acetate as the sole carbon and energy source and, in comparison to the wild type of C. glutamicum, showed very low specific activities of phosphotransacetylase, acetate kinase, isocitrate lyase, and malate synthase, irrespective of the presence of acetate in the medium. Comparative transcriptional cat fusion experiments revealed that this deregulation takes place at the level of transcription. By electrophoretic mobility shift analysis, purified His-tagged RamA protein was shown to bind specifically to the pta-ack and the aceA/aceB promoter regions, and deletion and mutation studies revealed in both regions two binding motifs each consisting of tandem A/C/TG4-6T/C or AC4-5A/G/T stretches separated by four or five arbitrary nucleotides. Our data indicate that RamA represents a novel LuxR-type transcriptional activator of genes involved in acetate metabolism of C. glutamicum.
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Graesser, Elizabeth, Maria Schwabe, Sean Akers, Cecilia Pascual-Garrido, John C. Clohisy, and Jeffrey J. Nepple. "ASSESSMENT OF ACETABULAR COVERAGE IN BORDERLINE ACETABULAR DYSPLASIA: ARE PLAIN RADIOGRAPHIC PARAMETERS ACCURATELY ESTIMATES OF THREE-DIMENSIONAL COVERAGE?" Orthopaedic Journal of Sports Medicine 8, no. 4_suppl3 (April 1, 2020): 2325967120S0020. http://dx.doi.org/10.1177/2325967120s00207.
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Introduction: Assessment of anterior acetabular coverage is commonly done with measurement of the anterior center edge angle (ACEA) or anterior wall index (AWI). This is particularly important in cases of borderline acetabular dysplasia where it may influence treatment decisions. However, the ACEA and AWI has been poorly validated. Purpose: The purpose of the current study was to investigate the correlation between plain radiographic measurements and three-dimensional femoral head coverage on low-dose CT in borderline acetabular dysplasia. Methods: Seventy consecutive hips with borderline acetabular dysplasia (LCEA 20-25°) were included in the current study. Radiographic evaluation was performed prospectively including LCEA, acetabular inclination, and AWI on AP pelvis radiographs, and ACEA on false profile radiographs. The mean LCEA was 22.1±1.4°, while the mean acetabular inclination was 10.3±3.3. All patients underwent low-dose pelvic CT assessment for preoperative planning. The radial acetabular coverage was calculated according to the standardized clock-face position [measured at 12:00 (lateral), 1:00, 2:00, 3:00 (anterior), and 4:00] as described by Larson et al. Statistical analysis determined the correlation between ACEA and radial coverage. Results: The mean ACEA in the group was 25.3±5.8° (range 10.1-43.9), with 16% having ACEA≤20° and 50% having ACEA≤25°. The mean radial coverages were 63.5%±1.7 (12:00), 60.7%±2.2 (1:00), 50.8%±3.2 (2:00), 37.0%±3.3 (3:00), and 27.9%±3.1 (4:00). The ACEA had poor correlation with radial coverage at all positions from 12:00 to 4:00 (range –0.068-0.173). The AWI had moderate correlation with radial coverage at 3:00 (PCC 0.499) and 4:00 (PCC 0.573). Comparing hips with an ACEA <20° versus >20°, there was no difference between the mean radial acetabular coverage at any position 12:00-4:00 (p=0.18-0.95). Comparing hips with an ACEA <25° versus >25°, there was no difference between the mean radial acetabular coverage at any position 12:00-4:00 (p=0.12-0.71). No significant difference in AWI was present between subgroups with normal and deficient radial coverage from 12:00 to 4:00 (p=0.09-0.72). Discussion: The current study demonstrates poor correlation of the ACEA measurement with true anterior femoral head coverage as evaluated at clock-face positions from 12:00 to 4:00. The AWI demonstrated moderate correlation for 3:00-4:00 coverage but fails to differentiate hips with normal and deficient coverage. In the setting of borderline acetabular dysplasia, anterior and anterolateral femoral coverage should be assessed via low-dose CT rather than ACEA or AWI.
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Warner, David S., Huijie Martin, Paula Ludwig, Alice McAllister, John F. W. Keana, and Eckard Weber. "In vivo Models of Cerebral Ischemia: Effects of Parenterally Administered NMDA Receptor Glycine Site Antagonists." Journal of Cerebral Blood Flow & Metabolism 15, no. 2 (March 1995): 188–96. http://dx.doi.org/10.1038/jcbfm.1995.24.
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Both in vitro and in vivo experiments have implicated extracellular glycine in the pathogenesis of ischemic brain damage. Recently, halogenated derivatives of quinoxaline-2,3-dione have been synthesized that possess bioavailability when parenterally administered and minimal psychotomimetic properties. Such compounds have allowed investigation into the efficacy of glycine receptor antagonism as a strategy for protection against cerebral ischemic insults. Rats underwent either 90 min of middle cerebral artery filament occlusion or 10 min of forebrain ischemia with recovery while receiving intraperitoneal injections of either a glycine receptor antagonist (ACEA-1021, ACEA-1031, or ACEA-1011) or vehicle (dimethyl sulfoxide). Both ACEA-1021 and ACEA-1031 reduced cerebral infarct volumes and were associated with a reduced incidence of hemiparesis resulting from MCA occlusion. ACEA-1011, administered in a smaller dose had no effect. In the forebrain ischemia model, glycine receptor antagonism had no effect on delayed neuronal necrosis in the hippocampal CA1 sector, neocortex, or caudoputamen. We conclude that pharmacologic antagonism of glycine at the strychnine-insensitive glycine receptor presents a neuroprotective profile similar to that previously observed for antagonists of glutamate at the N-methyl-d-aspartate complex with a potential for fewer side effects.
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Hagins, Jessica M., Jessica A. Scoffield, Sang-Jin Suh, and Laura Silo-Suh. "Influence of RpoN on isocitrate lyase activity in Pseudomonas aeruginosa." Microbiology 156, no. 4 (April 1, 2010): 1201–10. http://dx.doi.org/10.1099/mic.0.033381-0.
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Pseudomonas aeruginosa is the major aetiological agent of chronic pulmonary infections in patients with cystic fibrosis (CF). The metabolic pathways utilized by P. aeruginosa during these infections, which can persist for decades, are poorly understood. Several lines of evidence suggest that the glyoxylate pathway, which utilizes acetate or fatty acids to replenish intermediates of the tricarboxylic acid cycle, is an important metabolic pathway for P. aeruginosa adapted to the CF lung. Isocitrate lyase (ICL) is one of two major enzymes of the glyoxylate pathway. In a previous study, we determined that P. aeruginosa is dependent upon aceA, which encodes ICL, to cause disease on alfalfa seedlings and in rat lungs. Expression of aceA in PAO1, a P. aeruginosa isolate associated with acute infection, is regulated by carbon sources that utilize the glyoxyate pathway. In contrast, expression of aceA in FRD1, a CF isolate, is constitutively upregulated. Moreover, this deregulation of aceA occurs in other P. aeruginosa isolates associated with chronic infection, suggesting that high ICL activity facilitates adaptation of P. aeruginosa to the CF lung. Complementation of FRD1 with a PAO1 clone bank identified that rpoN negatively regulates aceA. However, the deregulation of aceA in FRD1 was not due to a knockout mutation of rpoN. Regulation of the glyoxylate pathway by RpoN is likely to be indirect, and represents a unique regulatory role for this sigma factor in bacterial metabolism.
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Chung, Jade C. S., Olena Rzhepishevska, Madeleine Ramstedt, and Martin Welch. "Type III secretion system expression in oxygen-limited Pseudomonas aeruginosa cultures is stimulated by isocitrate lyase activity." Open Biology 3, no. 1 (January 2013): 120131. http://dx.doi.org/10.1098/rsob.120131.
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Pseudomonas aeruginosa is an opportunistic human pathogen and a common cause of chronic infections in individuals with cystic fibrosis (CF). Oxygen limitation was recently reported to regulate the expression of a major virulence determinant in P. aeruginosa , the type III secretion system (T3SS). Here, we show that expression of the T3SS in oxygen-limited growth conditions is strongly dependent on the glyoxylate shunt enzyme, isocitrate lyase (ICL; encoded by aceA ), which was previously shown to be highly expressed in CF isolates. ICL-dependent regulation of the T3SS did not alter the expression level of the master transcriptional regulator, ExsA, but did affect expression of the T3 structural proteins, effectors and regulators (ExsC, ExsD and ExsE). An aceA mutant displayed enhanced biofilm formation during anaerobic growth, which suggested that AceA-dependent modulation of type III secretion might impinge upon the RetS/LadS signalling pathways. Indeed, our data suggest that RetS is able to mediate some of its effects through AceA, as expression of aceA in trans partially restored T3SS expression in a retS mutant. Our findings indicate that AceA is a key player in the metabolic regulation of T3SS expression during oxygen-limited growth of P. aeruginosa . To the best of our knowledge, this is the first demonstration that the T3SS can be regulated by factors that do not affect ExsA expression levels.
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Kelly, Sara, and Victoria Chapman. "Selective Cannabinoid CB1 Receptor Activation Inhibits Spinal Nociceptive Transmission In Vivo." Journal of Neurophysiology 86, no. 6 (December 1, 2001): 3061–64. http://dx.doi.org/10.1152/jn.2001.86.6.3061.
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Cannabinoid1 (CB1) receptors are located at CNS sites, including the spinal cord, involved in somatosensory processing. Analgesia is one of the tetrad of behaviors associated with cannabinoid agonists. Here, effects of a potent cannabinoid CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) on evoked responses of dorsal horn neurons in anesthetized rats were investigated. Extracellular recordings of convergent dorsal horn neurons were made in halothane anesthetized Sprague-Dawley rats ( n = 16). Effects of spinal application of ACEA on electrically evoked responses of dorsal horn neurons were studied. Mean maximal effects of 0.5, 5, 50, and 500 ng/50 μl ACEA on the C-fiber-mediated postdischarge response were 79 ± 6, 62 ± 10, and 54 ± 7% ( P < 0.01), 45 ± 6% ( P < 0.01), of control, respectively. ACEA (500 ng/50 μl) also reduced the C-fiber-evoked nonpotentiated responses of neurons (59 ± 9% of control, P < 0.05) and Aδ-fiber-evoked responses of neurons (68 ± 10% of control, P < 0.01). Minor effects of ACEA on Aβ-fiber-evoked responses were observed. Spinal pre-administration of the selective CB1 receptor antagonist SR141716A (0.01 μg/50 μl) significantly reduced effects of ACEA (500 ng/50 μl) on postdischarge responses of dorsal horn neurons. This study demonstrates that spinal CB1 receptors modulate the transmission of C- and Aδ-fiber-evoked responses in anesthetized rats; this may reflect pre- and/or postsynaptic effects of cannabinoids on nociceptive transmission. CB1 receptors inhibit synaptic release of glutamate in rat dorsolateral striatum, a similar mechanism of action may underlie the effects of ACEA on noxious evoked responses of spinal neurons reported here.
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Mozingo, Joseph D., Lindsay L. Schuring, Alexander J. Mortensen, Andrew E. Anderson, and Stephen K. Aoki. "Effect of Patient Positioning on Measurement of the Anterior Center-Edge Angle on False-Profile Radiographs and Its 3-Dimensional Mapping to the Acetabular Rim." Orthopaedic Journal of Sports Medicine 10, no. 2 (February 1, 2022): 232596712110738. http://dx.doi.org/10.1177/23259671211073834.
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Background: The anterior center-edge angle (ACEA) is used to quantify anterior coverage of the femoral head by the acetabulum. However, its measurement has not been evaluated in a manner consistent with routine use, and the precise 3-dimensional (3D) anatomic location where it measures coverage is not known. Purpose: To determine the effect of patient positioning on ACEA measurement reliability, magnitude, and 3D location. Study Design: Descriptive laboratory study. Methods: Included were 18 adults; 7 participants had cam morphology and femoroacetabular impingement syndrome, and 11 participants had no radiographic evidence of hip abnormalities and no history of hip pain or injuries. Ultimately, 3D femur and pelvis models were generated from computed tomography images. Radiographs were generated with the models in different degrees of pelvic rotation, tilt, and obliquity relative to the standard false-profile view. The ACEA was measured by 2 raters by selecting the location of the bone edge on each radiograph. Selections were projected onto the pelvis model and expressed as a clockface location on the acetabular rim. The clockface was mirrored on left hips to allow a direct comparison of locations between hips. Interrater and intrarater reliability were quantified via the intraclass correlation coefficient (ICC). The effect of position on ACEA measurements and clockface locations was determined via linear regression. Results: Intrarater and interrater reliability were excellent (ICC ≥0.97 for all). For every degree increase in rotation, tilt, and obliquity, the ACEA changed by +0.53°, +0.93°, and –0.04°, respectively. The mean clockface location (hour:minute:second) in the false-profile view was 2:09:32 ± 0:12:00 and changed by +0:02:08, –0:00:35, and –0:00:05 for every degree increase in rotation, tilt, and obliquity, respectively. Conclusion: ACEA measurements were reliable even with differences in patient positioning. Rotation and tilt were associated with notable changes in ACEA measurements. ACEA bone edge measurements mapped to the anterosuperior acetabular rim, typically in proximity to the anterior inferior iliac spine. Mapped location was most sensitive to rotation. Clinical Relevance: Pelvic rotation and tilt affected ACEA measurements, which could alter the clinical classification and treatment of borderline abnormalities. Rotation in particular must be well controlled during patient imaging to preserve measurement reliability and accuracy and to describe coverage from the intended 3D rim location.
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Petty, Margaret A., Philip M. Weintraub, and Kenneth I. Maynard. "ACEA 1021: Flip or Flop?" CNS Drug Reviews 10, no. 4 (June 7, 2006): 337–48. http://dx.doi.org/10.1111/j.1527-3458.2004.tb00031.x.
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Meybohm, Patrick, Philipp-Alexander Brand, Mike Ufer, Florian Thiemann, Markus Steinfath, Andrea Paris, Jens Scholz, and Berthold Bein. "Additive Interaction of the Cannabinoid Receptor I Agonist Arachidonyl-2-chloroethylamide with Etomidate in a Sedation Model in Mice." Anesthesiology 108, no. 4 (April 1, 2008): 669–74. http://dx.doi.org/10.1097/aln.0b013e318167aef7.
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Background Both propofol and volatile anesthetics have been reported to interact with the endocannabinoid system. The purpose of this study was to evaluate the effect of selective agonists for cannabinoid receptor types 1 and 2 on etomidate-induced sedation. Methods A controlled, blinded, experimental study was performed in 20 mice that received intraperitoneal injections of etomidate, the cannabinoid1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the cannabinoid2 receptor agonist JWH 133 alone, and both ACEA and JWH 133 combined with etomidate. The cannabinoid1 receptor antagonist AM 251 and the cannabinoid2 receptor antagonist AM 630 were administered 10 min before the delivery of ACEA and JWH 133, respectively. Each drug combination was applied to 6-8 mice of these 20 study animals. Sedation was monitored by a Rota-Rod (Ugo Basile, Comerio, Italy). Isobolographic analysis was used for evaluation of pharmacologic interaction. Results Single drug administration of etomidate and ACEA produced dose- and time-dependent decreased time on the Rota-Rod (P < 0.05). No sedative effect was seen after JWH 133. Etomidate-induced sedation was significantly increased and prolonged with ACEA (P < 0.05), but not with JWH 133. Isobolographic analysis revealed an additive interaction between ACEA and etomidate that was antagonized by the cannabinoid1 receptor antagonist AM 251. The cannabinoid1 receptor antagonist had no effect on etomidate alone. Conclusions Etomidate-induced sedation was increased and prolonged by activation of the cannabinoid1 receptor, but not of the cannabinoid2 receptor, in mice. However, this interaction was only additive.
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Nishiyama, Tomoki, Tony L. Yaksh, and Eckard Weber. "Effects of Intrathecal NMDA and Non-NMDA Antagonists on Acute Thermal Nociception and Their Interaction with Morphine." Anesthesiology 89, no. 3 (September 1, 1998): 715–22. http://dx.doi.org/10.1097/00000542-199809000-00023.
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Background N-methyl-D-aspartate (NDMA) antagonists have minimal effects on acute nociception but block facilitated states of processing. In contrast, the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists decrease acute noxious responses. Morphine (a mu-opioid agonist) can also decrease acute nociceptive processing. The authors hypothesized that the interaction between morphine and AMPA receptor antagonists would be synergistic, whereas morphine and NMDA antagonists show no such interaction in acute nociception. Methods Sprague-Dawley rats (weight, 250-300 g) were implanted with chronic lumbar intrathecal catheters and were assigned to receive one of several doses of morphine--ACEA 1021 (NMDA glycine site antagonist), ACEA 2085 (AMPA antagonist), AP-5 (NMDA antagonist), saline or vehicle--and were tested for their effect on the response latency using a 52.5 degrees C hot plate. The combinations of morphine and other agents also were tested. Results Intrathecal morphine (ED50:2 microg/95% confidence interval, 1-4 microg) and ACEA 2085 (6 ng/2-15 ng), but not AP-5 or ACEA 1021, yielded a dose-dependent increase in the thermal escape latency. A systematic isobolographic analysis was carried out between intrathecal morphine and ACEA 2085 using the ED50 dose ratio of 357:1. A potent synergy was observed with decreased side effects. Morphine dose-response curves were carried out for morphine and fixed doses of ACEA 1021 (12 microg) or AP-5 (10 microg). No synergistic interactions were noted. Conclusions Spinal mu-receptor activation and AMPA receptor antagonism showed a synergistic antinociception in response to an acute thermal stimulus. NMDA or NMDA glycine site antagonism had no effect alone nor did they display synergy with morphine. These results suggest an important direction for development of acute pain strategies may focus on the AMPA receptor.
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Odinokov, G. N., and K. A. Nikiforov. "Detection of New Variable DNA Loci That Distinguish Medievalis Biovar Strains of Plague Agent from the Strains of Other Biovars." Problems of Particularly Dangerous Infections, no. 4(114) (August 20, 2012): 47–48. http://dx.doi.org/10.21055/0370-1069-2012-4-47-48.
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Variable chromosome loci have been searched, that differentiate Yersinia pestis strains of medievalis from antiqua biovars. The strains of medievalis biovar are shown to possess two deletions – 183 and 70 bps. The first deletion, localized in the inter-gene region aceA – aceK is present in the majority of medievalis biovar strains, the second one, in the gene y1694 , is determined in all medievalis biovar strains isolated in the territory of Russia and neighboring countries.
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Navaza, Gonzalo. "Os topónimos Acea de Ama e O Xurés." Revista Galega de Filoloxía 5 (May 17, 2004): 141–62. http://dx.doi.org/10.17979/rgf.2004.5.0.5334.
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Este artigo ocúpase da historia e o significado de dous nomes de lugar galegos: Acea de Ama e O Xurés. O primeiro, denominación dunha localidade dos arredores da Coruña, é un topónimo composto do arabismo acea ‘muíño’, a preposición de e o hidrónimo prerromano AMA, que é o antigo nome da Ría do Burgo. O arabismo acea, que perdeu a consoante nasal etimolóxica, proporciona interesante información acerca dalgúns cambios fonéticos na historia do galego e a súa cronoloxía. Tanto o nome galego (O Xurés) coma o portugués (Gerês) dos coñecidos montes da raia seca proceden doutro hidrónimo prelatino que identificamos cos Originis, Oregines e Ocerensis rexistrados no Itinerarium Antonini e no mapa chamado do Ravenate, formas latinizadas ou deturpadas dun *OGERENSE ou *UGERENSE orixinario.
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Wall, Daniel M., Pamela S. Duffy, Chris DuPont, John F. Prescott, and Wim G. Meijer. "Isocitrate Lyase Activity Is Required for Virulence of the Intracellular Pathogen Rhodococcus equi." Infection and Immunity 73, no. 10 (October 2005): 6736–41. http://dx.doi.org/10.1128/iai.73.10.6736-6741.2005.
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ABSTRACT Rhodococcus equi is an important pathogen of foals, causing severe pyogranulomatous pneumonia. Virulent R. equi strains grow within macrophages, a process which remains poorly characterized. A potential source of carbon for intramacrophage R. equi is membrane lipid-derived fatty acids, which following β oxidation are assimilated via the glyoxylate bypass. To assess the importance of isocitrate lyase, the first enzyme of the glyoxylate bypass, in virulence of a foal isolate of R. equi, a mutant was constructed by a strategy of single homologous recombination using a suicide plasmid containing an internal fragment of the R. equi aceA gene encoding isocitrate lyase. Complementation of the resulting mutant with aceA showed that the mutant was specific for this gene. Assessment of virulence in a mouse macrophage cell line showed that the mutant was killed, in contrast to the parent strain. Studies in the liver of intravenously infected mice showed enhanced clearance of the mutant. When four 3-week-old foals were infected intrabronchially, the aceA mutant was completely attenuated, in contrast to the parent strain. In conclusion, the aceA gene was shown to be essential for virulence of R. equi, suggesting that membrane lipids may be an important source of carbon for phagocytosed R. equi.
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Lima, Ewelyne Miranda, Andrews Marques Nascimento, Girlandia Alexandre Brasil, Ieda Carneiro Kalil, Dominik Lenz, Denise Coutinho Endringer, Tadeu Uggere Andrade, and Nazaré Souza Bissoli. "Cardiopulmonary reflex, cardiac cytokines, and nandrolone decanoate: response to resistance training in rats." Canadian Journal of Physiology and Pharmacology 93, no. 11 (November 2015): 985–91. http://dx.doi.org/10.1139/cjpp-2015-0014.
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This study evaluated the effects of nandrolone associated with resistance training (RT) on cardiac cytokines, angiotensin-converting enzyme activity (ACEA), and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: CONT (received vehicle, no training); EXERC (RT: after one week of water adaptation, rats were exercised by jumping into water twice a week for 4 weeks), and ND+EXERC (received nandrolone decanoate 10 mg/kg, twice/week, i.m, associated with RT). The BJR was analysed by measuring bradycardic and hypotensive responses elicited by serotonin administration. Myocyte hypertrophy and matrix collagen deposition were determined by morphometric analysis of H&E and picrosirius red-stained samples, respectively. TNF-α and ACEA were also studied. RT promoted physiological myocyte hyrpertrophy but did not cause changes in the other parameters. The association of ND with RT increased myocyte hypertrophy, deposition of matrix type I collagen, TNF-α and ACEA; decreased IL-10, and impairment in the BJR were observed in ND+EXERC compared with CONT and EXERC. ND is associated with alterations in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cardiac cytokine imbalance, elevation of ACEA) and cardiac injury, even when combined with resistance training.
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Negro, Viviana, and Davide Mainero. "An integrated approach to energy use: the case study of the ACEA site." E3S Web of Conferences 119 (2019): 00023. http://dx.doi.org/10.1051/e3sconf/201911900023.
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Currently, ACEA utilises biogas obtained from the treatment of the organic fraction of municipal solid waste for thermal and electric energy recovery through endothermic engines (3 MW, in total). By 2020, the biogas produced at the site will no longer be used as a fuel for the combined heat and power units, but it is expected to feed a purification system in order to obtain a flow of biomethane to be injected into the natural gas network. This is part of the Italian strategy to achieve the Horizon 2020 European targets aimed at promoting the renewable production of transport fuels. In order to encourage sustainability and innovative prototype technologies, ACEA has also been involved in some European research projects, in particular for the conversion of biogas into other energy carriers. furthermore, ACEA ha recently built a flexible experimental platform that can used for the validation step of prototypes in an industrial field.
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Haspula, Dhanush, and Michelle A. Clark. "Contrasting Roles of Ang II and ACEA in the Regulation of IL10 and IL1β Gene Expression in Primary SHR Astroglial Cultures." Molecules 26, no. 10 (May 19, 2021): 3012. http://dx.doi.org/10.3390/molecules26103012.
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Angiotensin (Ang) II is well-known to have potent pro-oxidant and pro-inflammatory effects in the brain. Extensive crosstalk between the primary Ang II receptor, Ang type 1 receptor (AT1R), and the cannabinoid type 1 receptor (CB1R) has been demonstrated by various groups in the last decade. Since activation of glial CB1R has been demonstrated to play a key role in the resolution of inflammatory states, we investigated the role of Ang II (100 nM) and/or ACEA (10 nM), a potent CB1R-specific agonist in the regulation of inflammatory markers in astrocytes from spontaneously hypertensive rats (SHR) and Wistar rats. Astrocytes were cultured from brainstems and cerebellums of SHR and Wistar rats and assayed for IL1β and IL10 gene expression and secreted fraction, in treated and non-treated cells, by employing qPCR and ELISA, respectively. mRNA expression of both IL10 and IL1β were significantly elevated in untreated brainstem and cerebellar astrocytes isolated from SHR when compared to Wistar astrocytes. No changes were observed in the secreted fraction. While ACEA-treatment resulted in a significant increase in IL10 gene expression in Wistar brainstem astrocytes (Log2FC ≥ 1, p < 0.05), its effect in SHR brainstem astrocytes was diminished. Ang II treatment resulted in a strong inhibitory effect on IL10 gene expression in astrocytes from both brain regions of SHR and Wistar rats (Log2FC ≤ −1, p < 0.05), and an increase in IL1β gene expression in brainstem astrocytes from both strains (Log2FC ≥ 1, p < 0.05). Co-treatment of Ang II and ACEA resulted in neutralization of Ang II-mediated effect in Wistar brainstem and cerebellar astrocytes, but not SHR astrocytes. Neither Ang II nor ACEA resulted in any significant changes in IL10 or IL1β secreted proteins. These data suggest that Ang II and ACEA have opposing roles in the regulation of inflammatory gene signature in astrocytes isolated from SHR and Wistar rats. This however does not translate into changes in their secreted fractions.
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Bongaerts, Jan C. "Carbon Dioxide Emissions and Cars: An Environmental Agreement at EU Level." European Energy and Environmental Law Review 8, Issue 4 (April 1, 1999): 101–4. http://dx.doi.org/10.54648/eelr1999016.
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The EU's commitment to reducing carbon dioxide emissions and its "three pillars" strategy. The environmental agreement entered into with the European Automobile Manufacturers Association (ACEA); execution of the agreement; its contents; assessment by the Commission; the position of nonmembers of ACEA. Intermediate evaluation of the agreement. Reasons for adopting an environmental agreement rather than formulating legislation-uncertainty about the relative success of different technological measures, changes in marketing mix and keeping the global playing field level Conclusion that "the challenge will consist in putting the agreement into practice".
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Ruginsk, Silvia G., Fernanda M. V. Vechiato, Ernane T. Uchoa, Lucila L. K. Elias, and Jose Antunes-Rodrigues. "Type 1 cannabinoid receptor modulates water deprivation-induced homeostatic responses." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 309, no. 11 (December 1, 2015): R1358—R1368. http://dx.doi.org/10.1152/ajpregu.00536.2014.
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The present study investigated the type 1 cannabinoid receptor (CB1R) as a potential candidate to mediate the homeostatic responses triggered by 24 h of water deprivation, which constitutes primarily a hydroelectrolytic challenge and also significantly impacts energy homeostasis. The present results demonstrated for the first time that CB1R mRNA expression is increased in the hypothalamus of water-deprived (WD) rats. Furthermore, the administration of ACEA, a CB1R selective agonist, potentiated WD-induced dipsogenic effect, whereas AM251, a CB1R antagonist, attenuated not only water but also salt intake in response to WD. In parallel with the modulation of thirst and salt appetite, we confirmed that CB1Rs are essential for the development of appropriated neuroendocrine responses. Although the administration of ACEA or AM251 did not produce any effects on WD-induced arginine vasopressin (AVP) secretion, oxytocin (OXT) plasma concentrations were significantly decreased in WD rats treated with ACEA. At the genomic level, ACEA significantly decreased AVP and OXT mRNA expression in the hypothalamus of WD rats, whereas AM251 potentiated both basal and WD-induced stimulatory effects on the transcription of AVP and OXT genes. In addition, we showed that water deprivation alone upregulated proopiomelanocortin, Agouti-related peptide, melanin-concentrating hormone, and orexin A mRNA levels in the hypothalamus, and that CB1Rs regulate main central peptidergic pathways controlling food intake, being that most of these effects were also significantly influenced by the hydration status. In conclusion, the present study demonstrated that CB1Rs participate in the homeostatic responses regulating fluid balance and energy homeostasis during water deprivation.
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Vilches-Flores, Alonso, Astrid C. Hauge-Evans, Peter M. Jones, and Shanta J. Persaud. "Chronic activation of cannabinoid receptors in vitro does not compromise mouse islet function." Clinical Science 124, no. 7 (December 7, 2012): 467–78. http://dx.doi.org/10.1042/cs20120447.
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We have demonstrated previously that mouse and human islets express ECS (endocannabinoid system) elements, and that short-term activation of islet cannabinoid CB1r and CB2r (cannabinoid type 1 and 2 receptors respectively) stimulates insulin secretion in vitro. There is evidence that the ECS is overactive in Type 2 diabetes, impairing glucose homoeostasis, but little is known about whether it is implicated in islet dysfunction. Therefore the aim of the present study was to investigate the effect of chronic exposure of isolated mouse islets to cannabinoid receptor agonists on islet gene expression and function. Quantitative RT–PCR (reverse transcription–PCR) indicated that mRNAs encoding synthesis [NAPE-PLD (N-acyl-phosphatidyl ethanolamide-hydrolysing phospholipase D)] and degradation [FAAH (fatty acid amide hydrolase)] of the endocannabinoid AEA (anandamide) were the most abundant ECS elements in mouse islets, with much lower levels of CB1r, CB2r, DAGL (diacylglycerol lipase) and MAGL (monoacylglycerol lipase) mRNAs. Maintenance of islets for up to 7 days in the presence of the CB1r agonist ACEA [N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eiscosatetraenamide] or the CB2r agonist JWH015 [(2-methyl-1propyl-1H-indol3-yl)-1-napthalenylmethanone] did not compromise islet viability, as assessed by islet morphology and caspase activities, but there were some changes in mRNAs encoding ECS components. Neither glucose-stimulated insulin secretion nor acute insulin secretory responses to ACEA or JWH015 at 16 mM glucose were substantially modified by a 48 h or 7 day pre-exposure to these cannabinoid receptor agonists, but the stimulation of secretion at 3 mM glucose by 100 nM ACEA was significantly reduced after prolonged treatment with ACEA. Despite JWH015-induced reductions in islet glucagon content at 48 h and 7 days, there were no reductions in arginine-induced glucagon secretion from islets pre-exposed to JWH015 or ACEA. These data indicate that treatment of islets with agonists of CB1r and CB2r for up to 7 days does not have any major impact on islet function, suggesting that the impairments in glucose homoeostasis observed following overactivation of the ECS should be sought in relation to insulin resistance rather than β-cell dysfunction.
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Zhang, Dawei, Gang Zhang, Zongyu Li, and Bingsheng Li. "Activation of the cannabinoid receptor 1 by ACEA suppresses senescence in human primary chondrocytes through sirt1 activation." Experimental Biology and Medicine 243, no. 5 (February 14, 2018): 437–43. http://dx.doi.org/10.1177/1535370218757950.
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Senescence of chondrocytes and cartilage degeneration induced by the proinflammatory cytokine interleukin-1β is associated with the pathogenesis of osteoarthritis. The cannabinoid receptor 1 has been involved in the pathological development of various diseases. Here, we evaluated whether activation of cannabinoid receptor 1 using its selective agonist arachidonyl-2-chloroethylamide had an influence on cellular senescence induced by interleukin-1βin human chondrocytes. Our findings demonstrate that agonist arachidonyl-2-chloroethylamidedecreased senescence-associated β-galactosidase activity and cell cycle arrest in the G0/G1 phase induced by interleukin-1β. Importantly, our results display interleukin-1βtreatment significantly increased the expressions of senescence genes (caveolin-1, PAI-1 and p21), which were prevented by agonist arachidonyl-2-chloroethylamide treatment. However, it was noticed that these functions of agonist arachidonyl-2-chloroethylamide were abolished by the cannabinoid receptor 1 selective antagonist AM251, suggesting the involvement of cannabinoid receptor 1. Also, our results indicate that agonist arachidonyl-2-chloroethylamide enhanced the expression of sirt1. These findings suggest that activation of cannabinoid receptor 1 by agonist arachidonyl-2-chloroethylamide might have a protective effect against pro-inflammatory cytokines such as interleukin-1β-induced chondrocytes senescence in osteoarthritis patients. Impact statement Senescence of chondrocytes and cartilage degeneration induced by the proinflammatory cytokine interleukin-1β (IL-1β) are associated with the pathogenesis of osteoarthritis (OA). Here we found that: (a) the CB1 agonist ACEA abolished IL-1β-induced senescence and cell arrest in chondrocytes; (b) the CB1 agonist ACEA also abolished IL-1β-induced expression of caveolin-1, PAI-1, and p21; (c) ACEA regulated the expression of sirt1; (d) the inhibitory effects of ACEA on senescence were mediated by sirt1.
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Potenzieri, Carl, Thaddeus S. Brink, Cholawat Pacharinsak, and Donald A. Simone. "Cannabinoid Modulation of Cutaneous Aδ Nociceptors During Inflammation." Journal of Neurophysiology 100, no. 5 (November 2008): 2794–806. http://dx.doi.org/10.1152/jn.90809.2008.
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Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB1 and CB2). However, it is currently unknown if cannabinoids alter the response properties of nociceptors. In the present study, correlative behavioral and in vivo electrophysiological studies were conducted to determine if peripheral administration of the cannabinoid receptor agonists arachidonyl-2′-chloroethylamide (ACEA) or (R)-(+)-methanandamide (methAEA) could attenuate mechanical allodynia and hyperalgesia, and decrease mechanically evoked responses of Aδ nociceptors. Twenty-four hours after intraplantar injection of complete Freund's adjuvant (CFA), rats exhibited allodynia (decrease in paw withdrawal threshold) and hyperalgesia (increase in paw withdrawal frequency), which were attenuated by both ACEA and methAEA. The antinociceptive effects of these cannabinoids were blocked by co-administration with the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) but not with the CB2 receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl)methanone (AM630). ACEA and methAEA did not produce antinociception under control, non-inflamed conditions 24 h after intraplantar injection of saline. In parallel studies, recordings were made from cutaneous Aδ nociceptors from inflamed or control, non-inflamed skin. Both ACEA and methAEA decreased responses evoked by mechanical stimulation of Aδ nociceptors from inflamed skin but not from non-inflamed skin, and this decrease was blocked by administration of the CB1 receptor antagonist AM251. These results suggest that attenuation of mechanically evoked responses of Aδ nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB1 receptors during inflammation.
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Brand, P. A., P. Meybohm, J. Scholz, F. Renhof, and P. H. Tonner. "Interaction of the CB1 agonist ACEA and propofol." European Journal of Anaesthesiology 22, Supplement 34 (May 2005): 127. http://dx.doi.org/10.1097/00003643-200505001-00455.
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Li, Kui, Yi-mu Ji, Shang-dong Liu, Hai-chang Yao, Hang Li, Shuai You, and Si-si Shao. "ACEA: A Queueing Model-Based Elastic Scaling Algorithm for Container Cluster." Wireless Communications and Mobile Computing 2021 (May 26, 2021): 1–11. http://dx.doi.org/10.1155/2021/6621094.
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Elastic scaling is one of the techniques to deal with the sudden change of the number of tasks and the long average waiting time of tasks in the container cluster. The unreasonable resource supply may lead to the low comprehensive resource utilization rate of the cluster. Therefore, balancing the relationship between the average waiting time of tasks and the comprehensive resource utilization rate of the cluster based on the number of tasks is the key to elastic scaling. In this paper, an adaptive scaling algorithm based on the queuing model called ACEA is proposed. This algorithm uses the hybrid multiserver queuing model (M/M/s/K) to quantitatively describe the relationship among number of tasks, average waiting time of tasks, and comprehensive resource utilization rate of cluster and builds the cluster performance model, evaluation function, and quality of service (QoS) constraints. Particle swarm optimization (PSO) is used to search feasible solution space determined by the constraint relation of ACEA quickly, so as to improve the dynamic optimization performance and convergence timeliness of ACEA. The experimental results show that the algorithm can ensure the comprehensive resource utilization rate of the cluster while the average waiting time of tasks meets the requirement.
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Shelton, Trevor J., Monazzam Shafagh, Arash Calafi, Holly B. Leshikar, and Brian M. Haus. "PREOPERATIVE 3D MODELING AND PRINTING FOR GUIDING PERIACETABULAR OSTEOTOMY." Orthopaedic Journal of Sports Medicine 9, no. 7_suppl3 (July 1, 2021): 2325967121S0002. http://dx.doi.org/10.1177/2325967121s00026.
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Background: Achieving adequate acetabular correction in multiple planes is essential to the success of Periacetabular Osteotomy (PAO). Three-dimensional (3D) modeling and printing has the potential to improve preoperative planning by accurately guiding intraoperative correction. Hypothesis/Purpose: We, therefore, asked the following questions: 1) For a patient undergoing a PAO, does 3D-modeling with intraoperative 3D-printed models create a reproducible surgical plan to obtain predetermined parameters of correction including lateral center-edge angle (LCEA), anterior center-edge angle (ACEA), Tonnis angle, and femoral head extrusion index (FHEI), 2) Can 3D computer modeling accurately predict when a normalized FHEI can be achieved without the need for a concomitant femoral sided osteotomy? Methods: A retrospective review was conducted on forty-two (42) consecutive patients that underwent a PAO. 3D-modeling software was utilized to simulate a PAO in order to achieve normal LCEA, ACEA, Tonnis angle, and FHEI. If adequate FHEI was not achieved, a femoral osteotomy was simulated. 3D-models were printed as intraoperative guides. Preoperative, simulated, and postoperative ACEA, LCEA, Tonnis angle, and FHEI were measured and compared statistically. Results: 40 patients had a traditional PAO, and 2 had an anteverting-PAO. The simulated LCEA, ACEA, Tonnis angle, and FHEI were within a median difference of 3º, 1º, 1°, and 0% of postoperative values, respectively and showed no statistical difference. Of those that had a traditional PAO, all thirty-four (34) patients were correctly predicted to need a traditional acetabular sided correction alone and the other six (6) were correctly predicted to need a concomitant femoral osteotomy for a correct prediction in 100% of patients. Conclusion: This study demonstrated that in PAO, 3D-modeling and printing allow the surgeon to accurately create a reproducible surgical plan to obtain predetermined postoperative hip coverage parameters. This new technology has the potential to improve preoperative/intra-operative decision making for hip dysplasia and other complex disorders of the hip.
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Lansdown, Drew A., Kyle Kunze, Gift Ukwuani, Brian Robert Waterman, William H. Neal, and Shane Jay Nho. "Pre-operative and Post-Operative Alpha Angles are Significant Independent Predictors of Patient-Reported Outcome Measures at Two Years After Hip Arthroscopy." Orthopaedic Journal of Sports Medicine 6, no. 7_suppl4 (July 1, 2018): 2325967118S0017. http://dx.doi.org/10.1177/2325967118s00174.
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Objectives: Residual impingement after hip arthroscopy for femoroacetabular impingement (FAI) is a common cause for re-operation; however, the relationship between preoperative and postoperative radiographic parameters and patient-reported outcomes has not been defined. Methods: 749 consecutive patients were reviewed two years after primary hip arthroscopy. Patients undergoing revision surgery were excluded. Pre-operative and post-operative radiographs were analyzed to measure the alpha angle on standardized anteroposterior (AP) pelvis, Dunn-lateral, and false profile (FP) views and anterior and lateral center-edge angles (ACEA, LCEA). Univariate analysis evaluated the association between demographic variables, radiographic measures and hip outcome scores (Hip Outcome Score (HOS)-Activities of Daily Living (ADL), HOS-Sports Specific (SS), and Modified Harris Hip Score (mHHS)). Multivariate modeling was subsequently performed. Significance was defined as p<0.05. Results: 706 patients with mean age of 33.2±12.3 years and mean BMI 25.1± 5kg/m2 were included for final analysis. The alpha angle on the AP, Dunn-lateral, and FP views and the ACEA and LCEA decreased after surgery (p<0.001 for all). Significant univariate correlations with the postoperative HOS-ADL included age, BMI, pre-operative AP, FP, and Dunn and postoperative FP alpha angles. Postoperative HOS-SS was correlated with age, BMI, medial post-operative joint space width (JSW), pre-operative AP, FP, and Dunn and postoperative FP alpha angles, and pre-operative and post-operative (ACEA). Postoperative mHHS correlated with age, BMI, post-operative lateral JSW, pre-operative AP, FP, and Dunn and postoperative FP and Dunn alpha angles, and post-operative ACEA. Multivariate modeling (Table 2) demonstrated that preoperative and postoperative FP alpha angles were independent predictors of postoperative outcomes. Conclusion: Pre-operative and post-operative alpha angles were negatively correlated with the HOS-ADL, HOS-SS, and mHHS at 2 years after arthroscopic surgery for FAI. Specifically, pre-operative and postoperative FP alpha angles were independent predictors of postoperative outcomes. These results highlight the importance of resecting anterior cam lesions to prevent residual impingement and inferior outcomes. [Table: see text]
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Wang, Yingxu, Mehrdad Valipour, and Omar A. Zatarain. "Quantitative Semantic Analysis and Comprehension by Cognitive Machine Learning." International Journal of Cognitive Informatics and Natural Intelligence 10, no. 3 (July 2016): 13–28. http://dx.doi.org/10.4018/ijcini.2016070102.
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Knowledge learning is the sixth and the most fundamental category of machine learning mimicking the brain. It is recognized that the semantic space of machine knowledge is a hierarchical concept network (HCN), which can be rigorously represented by formal concepts in concept algebra and semantic algebra. This paper presents theories and algorithms of hierarchical concept classification by quantitative semantic analysis based on machine learning. Semantic equivalence between formal concepts is rigorously measured by an Algorithm of Concept Equivalence Analysis (ACEA). The semantic hierarchy among formal concepts is quantitatively determined by an Algorithm of Relational Semantic Classification (ARSC). Experiments applying Algorithms ACEA and ARSC on a set of formal concepts have been successfully conducted, which demonstrate a deep machine understanding of formal concepts and quantitative relations in the hierarchical semantic space by machine learning beyond human empirical perspectives.
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Graesser, Elizabeth, Maria Schwabe, Cecilia Pascual-Garrido, John C. Clohisy, and Jeffrey J. Nepple. "DEFINING THE BORDERLINE HIP: HIGH VARIABILITY IN ACETABULAR COVERAGE AND FEMORAL DEFORMITY." Orthopaedic Journal of Sports Medicine 8, no. 4_suppl3 (April 1, 2020): 2325967120S0021. http://dx.doi.org/10.1177/2325967120s00210.
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Introduction Borderline acetabular dysplasia is radiographically defined as a lateral center edge angle (LCEA) of 20-25 degrees. It is well accepted that some borderline hips have instability while others have primarily impingement. The optimal management of borderline dysplasia is challenging and particularly complex due to the anatomic variability that exists among patients but has not been well characterized. Purpose The purpose of this current study was to investigate the variability in hip deformity present on low-dose CT in a cohort of patients with symptomatic borderline acetabular dysplasia. Methods Seventy consecutive hips with borderline acetabular dysplasia undergoing surgical treatment were included in the current study. Radiographic evaluation included LCEA, acetabular inclination, anterior center edge angle (ACEA), and alpha angles on AP, Dunn, and frog views. All patients underwent low-dose pelvic CT for preoperative planning. Femoral deformity was assessed with femoral version, alpha angle (measured at 1:00 increments), and maximum alpha angle. Radial acetabular coverage was calculated according to standardized clock-face positions [measured from 8:00 (posterior) to 4:00 (anterior)] and defined as normal, under-coverage, or over-coverage relative to 1 SD from the mean of normative values. Results The mean LCEA was 22.1±1.4, while the mean acetabular inclination was 10.3±3.3. The mean ACEA in the group was 25.3±5.8 (range 10.1-43.9), with 16% having an ACEA ≤ 20 and 50% having an ACEA ≤ 25. The mean femoral version was 17.9° (range -4° to 59°). The mean maximal alpha angle was 57.2° (range 43° to 81°) with 61.4% greater than 55°. Lateral coverage (RAC at 12:00) was deficient in 74.1% of cases. Anterior coverage (RAC at 2:00) was highly variable with 17.1% under-coverage, 72.9% normal, and 10.0% over-coverage. Posterior coverage (RAC at 10:00) was also highly variable with 30.0% under-coverage, 62.9% normal, and 7.1% over-coverage. The three most common patterns of coverage were: isolated lateral under-coverage (31.4%), normal coverage (18.6%), and lateral and posterior under-coverage (17.1%). Discussion Patients with borderline acetabular dysplasia demonstrate highly variable three-dimensional deformities including anterior, lateral, and posterior acetabular coverage, femoral version, and alpha angle. Comprehensive deformity characterization in the population is important to guide diagnosis and treatment decisions.
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Schwabe, Maria, Cecilia Pascual-Garrido, John Clohisy, and Elizabeth Graesser Jeffrey Nepple. "Defining the Borderline Hip: High Variability in Acetabular Coverage and Femoral Deformity." Orthopaedic Journal of Sports Medicine 8, no. 7_suppl6 (July 1, 2020): 2325967120S0034. http://dx.doi.org/10.1177/2325967120s00346.
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Objectives: Borderline acetabular dysplasia is radiographically defined as a lateral center edge angle (LCEA) of 20-25 degrees. It is well accepted that some borderline hips have instability while others have primarily impingement. The optimal management of borderline dysplasia is challenging and particularly complex due to the anatomic variability that exists among patients but has not been well characterized. The purpose of this current study was to investigate the variability in hip deformity present on low-dose CT in a cohort of patients with symptomatic borderline acetabular dysplasia. Methods: Seventy consecutive hips with borderline acetabular dysplasia undergoing surgical treatment were included in the current study. Radiographic evaluation included LCEA, acetabular inclination, anterior center edge angle (ACEA), and alpha angles on AP, Dunn, and frog views. All patients underwent low-dose pelvic CT for preoperative planning. Femoral deformity was assessed with femoral version, alpha angle (measured at 1:00 increments), and maximum alpha angle. Radial acetabular coverage was calculated according to standardized clockface positions [measured from 8:00 (posterior) to 4:00 (anterior)] and defined as normal, undercoverage, or overcoverage relative to 1 SD from the mean of normative values. Results: The mean LCEA was 22.1+1.4, while the mean acetabular inclination was 10.3+3.3. The mean ACEA in the group was 25.3+5.8 (range 10.1-43.9), with 16% having an ACEA < 20 and 50% having an ACEA < 25. The mean femoral version was 17.9° (range -4° to 59°). The mean maximal alpha angle was 57.2° (range 43° to 81°) with 61.4% greater than 55°. Lateral coverage (RAC at 12:00) was deficient in 74.1% of cases. Anterior coverage (RAC at 2:00) was highly variable with 17.1% undercoverage, 72.9% normal, and 10.0% overcoverage. Posterior coverage (RAC at 10:00) was also highly variable with 30.0% undercoverage, 62.9% normal, and 7.1% overcoverage. The three most common patterns of coverage were: isolated lateral undercoverage (31.4%), normal coverage (18.6%), and lateral and posterior undercoverage (17.1%). Conclusion: Patients with borderline acetabular dysplasia demonstrate highly variable three-dimensional deformities including anterior, lateral, and posterior acetabular coverage, femoral version, and alpha angle. Comprehensive deformity characterization in the population is important to guide diagnosis and treatment decisions. [Figure: see text][Figure: see text][Figure: see text]
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Lee, Jin-Ho, Dong-Eun Lee, Bheong-Uk Lee, and Hak-Sung Kim. "Global Analyses of Transcriptomes and Proteomes of a Parent Strain and an l-Threonine-Overproducing Mutant Strain." Journal of Bacteriology 185, no. 18 (September 15, 2003): 5442–51. http://dx.doi.org/10.1128/jb.185.18.5442-5451.2003.
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ABSTRACT We compared the transcriptome, proteome, and nucleotide sequences between the parent strain Escherichia coli W3110 and the l-threonine-overproducing mutant E. coli TF5015. DNA macroarrays were used to measure mRNA levels for all of the genes of E. coli, and two-dimensional gel electrophoresis was used to compare protein levels. It was observed that only 54 of 4,290 genes (1.3%) exhibited differential expression profiles. Typically, genes such as aceA, aceB, icdA, gltA, glnA, leu operon, proA, thrA, thrC, and yigJ, which are involved in the glyoxylate shunt, the tricarboxylic acid cycle, and amino acid biosynthesis (l-glutamine, l-leucine, proline, and l-threonine), were significantly upregulated, whereas the genes dadAX, hdeA, hdeB, ompF, oppA, oppB, oppF, yfiD, and many ribosomal protein genes were downregulated in TF5015 compared to W3110. The differential expression such as upregulation of thr operon and expression of yigJ would result in an accumulation of l-threonine in TF5015. Furthermore, two significant mutations, thrA345 and ilvA97, which are essential for overproduction of l-threonine, were identified in TF5015 by the sequence analysis. In particular, expression of the mutated thrABC (pATF92) in W3110 resulted in a significant incremental effect on l-threonine production. Upregulation of aceBA and downregulation of b1795, hdeAB, oppA, and yfiD seem to be linked to a low accumulation of acetate in TF5015. Such comprehensive analyses provide information regarding the regulatory mechanism of l-threonine production and the physiological consequences in the mutant stain.
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Kim, Yang Re, Shaun R. Brinsmade, Zheng Yang, Jorge Escalante-Semerena, and Joshua Fierer. "Mutation of Phosphotransacetylase but Not Isocitrate Lyase Reduces the Virulence of Salmonella enterica Serovar Typhimurium in Mice." Infection and Immunity 74, no. 4 (April 2006): 2498–502. http://dx.doi.org/10.1128/iai.74.4.2498-2502.2006.
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ABSTRACT A phosphotransacetylase (pta) mutant of Salmonella enterica serovar Typhimurium was attenuated in mice but survived normally in macrophages. Complementation of the pta mutation in trans restored virulence. An isocitrate lyase (aceA) mutant was virulent, so the inability to use acetate as a sole carbon source does not explain the phenotype.
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Zolotov, V. A. "New requirements for the properties of promising oils for automotive diesel and gasoline engines and methods of their testing." World of petroleum products 04 (2022): 42–45. http://dx.doi.org/10.32758/2782-3040-2022-0-4-42-45.
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Analytical information is presented on the development and implementation of new technical requirements for the performance properties of motor oils and new methods of testing them in the specifications for promising automotive engines, taking into account global trends in environmental protection. Taking into account the latest diesel designs, the European Association of Automakers (Association des Constructeures Europe'enes d’ Automobiles - ACEA) has updated the specifications for engine oils for high-power diesels this year, including low-viscosity oils with an extended shift interval. The changes do not directly concern the assessment of the energy-saving properties of motor oils - saving fuel consumption when using them. ACEA is updating its specifications for heavy-duty heavy-duty diesel engines three years later than their originally planned adoption by the end of 2018. Two new oil categories E8 and E11 have been added to the 2022 ACEA specification with simultaneous replacement of categories E6 and E9, respectively, declared obsolete. The possibility of using potentially new methods for evaluating their properties - the ability of oils to reduce high-temperature engine wear and the amount of deposits in the turbocharger - is being considered when testing oils of the new GF-7 category. The use of upgraded methods is proposed: a new Noack test to determine the volatility of oils to assess their volatility and consumption, an updated Ford method to assess the pre-ignition of the fuel mixture at low speeds and high torque to ensure engine protection during the service life of the oil. Finally, a number of Original Equipment manufacturers (Original Equipment Manufacturer - OEM) assume the use of low–viscosity oils of classes 0W-8 and 0W-12 according to SAE for their engines, and these brands are likely to be included in the list of tested oils of the GF-7 category according to the new ILSAC specification.
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Trampert, Stefan. "Entwicklungstrends von Motor und Getriebe vor dem Hintergrund der ACEA-Selbstverpflichtung." ATZ - Automobiltechnische Zeitschrift 108, no. 6 (June 2006): 466–74. http://dx.doi.org/10.1007/bf03221795.
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Abdian, Patricia L., Annemarie C. Lellouch, Catherine Gautier, Luis Ielpi, and Roberto A. Geremia. "Identification of Essential Amino Acids in the Bacterial α-Mannosyltransferase AceA." Journal of Biological Chemistry 275, no. 51 (September 21, 2000): 40568–75. http://dx.doi.org/10.1074/jbc.m007496200.
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Geremia, R. A., M. Roux, D. U. Ferreiro, R. Dauphin-Dubois, A. C. Lellouch, and L. Ielpi. "Expression and biochemical characterisation of recombinant AceA, a bacterial α-mannosyltransferase." Molecular and General Genetics MGG 261, no. 6 (August 1999): 933–40. http://dx.doi.org/10.1007/s004380051040.
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Sebbane, Florent, Clayton O. Jarrett, Jan R. Linkenhoker, and B. Joseph Hinnebusch. "Evaluation of the Role of Constitutive Isocitrate Lyase Activity in Yersinia pestis Infection of the Flea Vector and Mammalian Host." Infection and Immunity 72, no. 12 (December 2004): 7334–37. http://dx.doi.org/10.1128/iai.72.12.7334-7337.2004.
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ABSTRACT Yersinia pestis, unlike the closely related Yersinia pseudotuberculosis, constitutively produces isocitrate lyase (ICL). Here we show that the Y. pestis aceA homologue encodes ICL and is required for growth on acetate but not for flea infection or virulence in mice. Thus, deregulation of the glyoxylate pathway does not underlie the recent adaptation of Y. pestis to arthropod-borne transmission.
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Höner Zu Bentrup, Kerstin, Andras Miczak, Dana L. Swenson, and David G. Russell. "Characterization of Activity and Expression of Isocitrate Lyase in Mycobacterium avium andMycobacterium tuberculosis." Journal of Bacteriology 181, no. 23 (December 1, 1999): 7161–67. http://dx.doi.org/10.1128/jb.181.23.7161-7167.1999.
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ABSTRACT Analysis by two-dimensional gel electrophoresis revealed thatMycobacterium avium expresses several proteins unique to an intracellular infection. One abundant protein with an apparent molecular mass of 50 kDa was isolated, and the N-terminal sequence was determined. It matches a sequence in the M. tuberculosisdatabase (Sanger) with similarity to the enzyme isocitrate lyase of both Corynebacterium glutamicum and Rhodococcus fascians. Only marginal similarity was observed between this open reading frame (ORF) (termed icl) and a second distinct ORF (named aceA) which exhibits a low similarity to other isocitrate lyases. Both ORFs can be found as distinct genes in the various mycobacterial databases recently published. Isocitrate lyase is a key enzyme in the glyoxylate cycle and is essential as an anapleurotic enzyme for growth on acetate and certain fatty acids as carbon source. In this study we express and purify Icl, as well as AceA proteins, and show that both exhibit isocitrate lyase activity. Various known inhibitors for isocitrate lyase were effective. Furthermore, we present evidence that in both M. avium and M. tuberculosis the production and activity of the isocitrate lyase is enhanced under minimal growth conditions when supplemented with acetate or palmitate.
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Franck, William L., Woo-Suk Chang, Jing Qiu, Masayuki Sugawara, Michael J. Sadowsky, Stephanie A. Smith, and Gary Stacey. "Whole-Genome Transcriptional Profiling of Bradyrhizobium japonicum during Chemoautotrophic Growth." Journal of Bacteriology 190, no. 20 (August 8, 2008): 6697–705. http://dx.doi.org/10.1128/jb.00543-08.
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ABSTRACT Bradyrhizobium japonicum is a facultative chemoautotroph capable of utilizing hydrogen gas as an electron donor in a respiratory chain terminated by oxygen to provide energy for cellular processes and carbon dioxide assimilation via a reductive pentose phosphate pathway. A transcriptomic analysis of B. japonicum cultured chemoautotrophically identified 1,485 transcripts, representing 17.5% of the genome, as differentially expressed when compared to heterotrophic cultures. Genetic determinants required for hydrogen utilization and carbon fixation, including the uptake hydrogenase system and components of the Calvin-Benson-Bassham cycle, were strongly induced in chemoautotrophically cultured cells. A putative isocitrate lyase (aceA; blr2455) was among the most strongly upregulated genes, suggesting a role for the glyoxylate cycle during chemoautotrophic growth. Addition of arabinose to chemoautotrophic cultures of B. japonicum did not significantly alter transcript profiles. Furthermore, a subset of nitrogen fixation genes was moderately induced during chemoautotrophic growth. In order to specifically address the role of isocitrate lyase and nitrogenase in chemoautotrophic growth, we cultured aceA, nifD, and nifH mutants under chemoautotrophic conditions. Growth of each mutant was similar to that of the wild type, indicating that the glyoxylate bypass and nitrogenase activity are not essential components of chemoautotrophy in B. japonicum.
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Jo, Jae-Hyung, Hye-Young Seol, Yun-Bom Lee, Min-Hong Kim, Hyung-Hwan Hyun, and Hyune-Hwan Lee. "Disruption of genes for the enhanced biosynthesis of α-ketoglutarate in Corynebacterium glutamicum." Canadian Journal of Microbiology 58, no. 3 (March 2012): 278–86. http://dx.doi.org/10.1139/w11-132.
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The development of microbial strains for the enhanced production of α-ketoglutarate (α-KG) was investigated using a strain of Corynebacterium glutamicum that overproduces of l-glutamate, by disrupting three genes involved in the α-KG biosynthetic pathway. The pathways competing with the biosynthesis of α-KG were blocked by knocking out aceA (encoding isocitrate lyase, ICL), gdh (encoding glutamate dehydrogenase, l-gluDH), and gltB (encoding glutamate synthase or glutamate-2-oxoglutarate aminotransferase, GOGAT). The strain with aceA, gltB, and gdh disrupted showed reduced ICL activity and no GOGAT and l-gluDH activities, resulting in up to 16-fold more α-KG production than the control strain in flask culture. These results suggest that l-gluDH is the key enzyme in the conversion of α-KG to l-glutamate; therefore, prevention of this step could promote α-KG accumulation. The inactivation of ICL leads the carbon flow to α-KG by blocking the glyoxylate pathway. However, the disruption of gltB did not affect the biosynthesis of α-KG. Our results can be applied in the industrial production of α-KG by using C. glutamicum as producer.
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Nelson, Kimberlyn, Fu-Sheng Wang, E. Fidelma Boyd, and Robert K. Selander. "Size and Sequence Polymorphism in the Isocitrate Dehydrogenase Kinase/Phosphatase Gene (aceK) and Flanking Regions in Salmonella enterica and Escherichia coli." Genetics 147, no. 4 (December 1, 1997): 1509–20. http://dx.doi.org/10.1093/genetics/147.4.1509.
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Abstract The sequence of aceK, which codes for the regulatory catalytic enzyme isocitrate dehydrogenase kinase/phosphatase (IDH K/P), and sequences of the 5′ flanking region and part or all of the 3′ flanking region were determined for 32 strains of Salmonella enterica and Escherichia coli. In E. coli, the aceK gene was 1734 bp long in 13 strains, but in three strains it was 12 bp shorter and the stop codon was TAA rather than TGA. Strains with the shorter aceK lacked an open reading frame (f728) downstream between aceK and iclR that was present, in variable length, in the other strains. Among the 72 ECOR strains, the truncated aceK gene was present in all isolates of the B2 group and half of those of the D group. Other variant conditions included the presence of IS1 elements in two strains and large deletions in two strains. The aceK-aceA intergenic region varied in length from 48 to 280 bp in E. coli, depending largely on the number of repetitive extragenic palindromic (REP) sequences present. Among the ECOR strains, the number of REP elements showed a high degree of phylogenetic association, and sequencing of the region in the ECOR strains permitted partial reconstruction of its evolutionary history. In S. enterica, the normal length of aceK was 1752 bp, but three other length variants, ranging from 1746 to 1785 bp, were represented in five of the 16 strains examined. The flanking intergenic regions showed relatively minor variation in length and sequence. The occurrence of several nonrandom patterns of distribution of polymorphic synonymous nucleotide sites indicated that intragenic recombination of horizontally exchanged DNA has contributed to the generation of allelic diversity at the aceK locus in both species.
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Zhou, Xuan, Le Yang, Xiaoting Fan, Xinhao Zhao, Na Chang, Lin Yang, and Liying Li. "Neutrophil Chemotaxis and NETosis in Murine Chronic Liver Injury via Cannabinoid Receptor 1/Gαi/o/ROS/p38 MAPK Signaling Pathway." Cells 9, no. 2 (February 5, 2020): 373. http://dx.doi.org/10.3390/cells9020373.
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Neutrophils play an essential role in the control of inflammatory diseases. However, whether cannabinoid receptors (CBs) play a role in neutrophil chemotaxis and NETosis in sterile liver inflammation remains unknown. The expression of marker genes on neutrophils was characterized by FACS, immunofluorescence, qRT-PCR, and Western blot. The amount of neutrophils was significantly elevated from 7 days and reached the peak at 2 weeks in carbon tetrachloride (CCl4)-treated mouse liver. The mRNA expression of neutrophil marker Ly6G had positive correlation with CB1 and CB2 expression in injured liver. In vitro CBs were abundantly expressed in isolated neutrophils and CB1 agonist ACEA promoted the chemotaxis and cytoskeletal remodeling, which can be suppressed by CB1 antagonist AM281. Moreover, ACEA induced NETosis, myeloperoxidase release from lysosome and ROS burst, indicating neutrophil activation, via Gαi/o. Conversely, CB2 agonist JWH133 had no effect on neutrophil function. ROS and p38 MAPK signaling pathways were involved in CB1-mediated neutrophil function, and ROS was upstream of p38 MAPK. CB1 blockade in vivo significantly attenuated neutrophil infiltration and liver inflammation in CCl4-treated mice. Taken together, CB1 mediates neutrophil chemotaxis and NETosis via Gαi/o/ROS/p38 MAPK signaling pathway in liver inflammation, which represents an effective therapeutic strategy for liver diseases.
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Koay, Luan C., Rachael J. Rigby, and Karen L. Wright. "Cannabinoid-induced autophagy regulates suppressor of cytokine signaling-3 in intestinal epithelium." American Journal of Physiology-Gastrointestinal and Liver Physiology 307, no. 2 (July 15, 2014): G140—G148. http://dx.doi.org/10.1152/ajpgi.00317.2013.
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Autophagy is a catabolic process involved in homeostatic and regulated cellular protein recycling and degradation via the lysosomal degradation pathway. Emerging data associate impaired autophagy, increased activity in the endocannabinoid system, and upregulation of suppressor of cytokine signaling-3 (SOCS3) protein expression during intestinal inflammation. We have investigated whether these three processes are linked. By assessing the impact of the phytocannabinoid cannabidiol (CBD), the synthetic cannabinoid arachidonyl-2′-chloroethylamide (ACEA), and the endocannabinoid N-arachidonoylethanolamine (AEA) on autophagosome formation, we explored whether these actions were responsible for cyclic SOCS3 protein levels. Our findings show that all three cannabinoids induce autophagy in a dose-dependent manner in fully differentiated Caco-2 cells, a model of mature intestinal epithelium. ACEA and AEA induced canonical autophagy, which was cannabinoid type 1 receptor-mediated. In contrast, CBD was able to bypass the cannabinoid type 1 receptor and the canonical pathway to induce autophagy, albeit to a lesser extent. Functionally, all three cannabinoids reduced SOCS3 protein expression, which was reversed by blocking early and late autophagy. In conclusion, the regulatory protein SOCS3 is regulated by autophagy, and cannabinoids play a role in this process, which could be important when therapeutic applications for the cannabinoids in inflammatory conditions are considered.
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Brennan, Timothy J., and Peter K. Zahn. "Effect of Intrathecal ACEA-1021 in a Rat Model for Postoperative Pain." Journal of Pain 1, no. 4 (January 2000): 279–84. http://dx.doi.org/10.1054/jpai.2000.8921.
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Tsang, Q. K., Y. Yu, A. E. Lomax, S. Vanner, and D. E. Reed. "A239 COMBINED CANNABINOID RECEPTOR 1 AND MU-OPIOID RECEPTOR AGONISTS SYNERGISTICALLY INHIBIT VISCERAL PAIN IN VIVO WITHOUT ADVERSE SIDE EFFECTS OR TOLERANCE." Journal of the Canadian Association of Gastroenterology 5, Supplement_1 (February 21, 2022): 131–32. http://dx.doi.org/10.1093/jcag/gwab049.238.
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Abstract Background Previously we have shown that both cannabinoid 1 receptor (CB1R) and mu-opioid receptor (MOR) agonists inhibit mechanosensitivity of colonic nociceptive nerves. However, it is unknown whether agonists of cannabinoid and opioid receptors have a synergistic interaction, such that very low doses of these agonists can be employed to reduce visceral pain and side effects. Aims To determine the effects of combined cannabinoid and opioid receptor agonists on visceral pain and its side effects. Methods Telemetric transmitters were surgically implanted into the abdominal cavity of C57/BL6 mice, with electrodes sutured to the external oblique muscle to measure the visceromotor response (VMR) to colorectal distention using a 4F arterial embolectomy catheter (volume range 20–80 µL). Mice were injected intraperitoneally with vehicle, arachidonyl-2’-chloroethylamide (ACEA), a selective CB1R agonist (0.3, 1, 3 mg/kg), HU-308, a selective CB2R agonist (0.3, 1, 3mg/kg), morphine, a MOR agonist (0.3, 3 mg/kg), or a combination, 30-minutes prior to distention. To assess side effects, pulse oximetry, heart rate, fecal pelleting, and locomotion (via an open-field maze) were measured. Data was analyzed with one or two-way ANOVA with post-hoc Bonferroni multiple comparisons test. Results ACEA dose-dependently reduced VMR (P<0.01 vs. vehicle, N=5); at the 80 µL distention, reductions of 35% (P<0.01) and 62% (P<0.01) were observed for 1 mg/kg and 3 mg/kg respectively. In contrast, HU-308 did not reduce VMR at any dose (P=0.17, N=8). Morphine (0.3 mg/kg) did not reduce VMR (P>0.99), while a higher dose (3 mg/kg) attenuated VMR (P<0.01 vs. vehicle, N=5); reductions of 32% (P<0.01) and 61% (P<0.01) at 60 and 80 µL distentions respectively. Interestingly, a combination of sub-analgesic doses of ACEA (0.3 mg/kg) and morphine (0.3 mg/kg) significantly reduced VMR (P<0.01 vs vehicle, N=5); compared to vehicle, VMR was reduced by 21% at 40 µL (P<0.05), 27% at 60 µL (P<0.01) and 60% at 80 µL (P<0.01). Chronic administration (2x/day for 6 days) of this combination did not alter the magnitude of its inhibitory effect (P=0.67, N=5), suggesting tolerance did not develop. While analgesic doses of morphine (3mg/kg) decreased oxygen saturation (P<0.01), heart rate (P<0.01) and fecal pelleting (i.e., GI motility; P<0.05), the sub-analgesic combination of ACEA and morphine had no effect (P>0.99 for all, N=5). Locomotion was unchanged by the agonists alone or combined (P=0.17). Conclusions A combination of sub-analgesic doses of CB1R and MOR agonists significantly inhibits visceral pain in vivo, without development of sides effects or tolerance with chronic use. Thus, combining low doses of CB1R and MOR agonists may be an effective visceral pain management strategy. Funding Agencies NSERC