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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: β-Arrestins are key negative regulators and scaffolds of G protein-coupled receptor (GPCR) signalling. β-Arrestin1 and β-arrestin2 preferentially bind to the phosphorylated GPCRs in response to agonist stimulation, resulting in receptor internalization and desensitization. The critical roles of GPCR kinases (GRKs)-catalyzed receptor phosphorylation and interaction of β-arrestins with the phosphorylated receptor in receptor internalization are well established. However, emerging evidence suggests that an agonist-stimulated internalization mechanism that is independent of receptor phosphorylation may also be employed in some cases, although the molecular mechanism for the phosphorylation-independent GPCR internalization is not clear. The current study investigated the role of receptor phosphorylation and the involvement of different β-arrestin subtypes in agonist-induced δ-opioid receptor (DOR) internalization in HEK293 cells. Results from flow cytometry, fluorescence microscopy, and surface biotin labelling experiments showed that elimination of agonist-induced DOR phosphorylation by mutation GRK binding or phosphorylation sites only partially blocked agonist-induced receptor internalization, indicating the presence of an agonist-induced, GRK-independent mechanism for DOR internalization. Fluorescence and co-immunoprecipitation studies indicated that both the wild-type DOR and the phosphorylation-deficient mutant receptor could bind and recruit β-arrestin1 and β-arrestin2 to the plasma membrane in an agonist-stimulated manner. Furthermore, internalization of both the wild-type and phosphorylation-deficient receptors was increased by overexpression of either type of β-arrestins and blocked by dominant-negative mutants of β-arrestin-mediated internalization, demonstrating that both phosphorylation-dependent and -independent internalization require β-arrestin. Moreover, double-stranded RNA-mediated interference experiments showed that either β-arrestin1 or β-arrestin2 subtype-specific RNAi only partially inhibited agonist-induced internalization of the wild-type DOR. However, agonist-induced internalization of the phosphorylation-deficient DOR was not affected by β-arrestin1-specific RNAi but was blocked by RNAi against β-arrestin2 subtype. These data indicate that endogenous β-arrestin1 functions exclusively in the phosphorylation-dependent receptor internalization, whereas endogenous β-arrestin2, but not β-arrestin1, is required for the phosphorylation-independent receptor internalization. These results thus provide the first evidence of different requirement for β-arrestin isoforms in the agonist induced phosphorylation-dependent and -independent GPCR internalization.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 17 (2003), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The present study investigated the effects of intra-CA1 infusion of d,l-propranolol, the β-adrenergic antagonist, on memory for contextual fear conditioning. d,l-Propranolol administered 5 min (‘0 h’) postconditioning impaired long-term but not short-term contextual fear memory, while it was ineffective when administered 6 h postconditioning, suggesting that there is a time window for β-adrenoceptors to play a role. Thus, we conclude that β-adrenoceptors in area CA1 are involved in regulating consolidation of contextual fear memory, with ‘0 h’ but not 6 h post-training, a sensitive time point for the β-adrenergic involvement.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To explore the role of the ventral prefrontal cortex (PFv) in conditional visuomotor learning, we infused locally bicuculline, a GABAergic antagonist, into the PFv of two monkeys, well trained on a two-problem visuomotor task. The task required the monkeys to execute one of two motor actions (moving a handle to the left or to the right) in response to one of two familiar visual patterns (circle or triangle). The two patterns mapped 1 : 1 onto the two motor actions: for each pattern one and only one motor action was scored, correct and reinforced. In contrast to these sessions with familiar patterns, in the learning sessions the monkeys were presented with one or two novel patterns and required to learn the arbitrarily determined associations between these patterns and the two motor actions. We found that bilateral infusion of bicuculline into PFv dramatically impaired the monkeys' ability to learn novel pattern–response associations: the trials and errors to criterion (90% correct) increased significantly. The errors were mainly an inability to apply ‘Win-Stay’, ‘Lose-Shift’ and ‘Change-Shift’ strategies. There was no effect on the monkeys' performance in responding to familiar patterns. Similar infusion of bicuculline into the dorsal prefrontal cortex was without effect on either novel-pattern learning or familiar-pattern performance. We conclude that the ventral prefrontal cortex is necessary for learning new visuomotor associations, but has less importance, if any, for performing pre-established ones.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 117 (1997), S. 207-218 
    ISSN: 1432-1106
    Keywords: Key words Putamen ; Dopamine ; Iontophoresis ; Go/Nogo task ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Using multibarreled glass micropipettes, we recorded single-unit activity in the putamen, and iontophoretically applied D1 and D2 dopamine receptor agonists (SKF38393, quinpirole) and antagonists (SCH23390, sulpiride) while two monkeys were performing a delayed Go/Nogo task. The putaminal neurons exhibited changes in activity during various task periods (hold, cue, delay, response, and reward periods) in both Go and Nogo trials. Of 296 task-related putaminal neurons, 87 showed activity changes in Go trials only (Go type), 74 in Nogo trials only (Nogo type), 99 in both trials during the same task periods (Both type), and 36 in both trials but during different task periods (Different type). These 296 neurons were examined as regards the effects of both D1 and D2 agonists and/or antagonists, and 234 neurons responded to either D1- or D2-related substances or both. Among them 41% of neurons responded to the D1 substances only (D1 group), 36% responded to the D2 substances only (D2 group), and 23% responded to both D1 and D2 substances (D1D2 group). During the iontophoretic application of the D1 and D2 substances, most of the responding neurons changed their task-related activity but not their baseline firing rates. The D1 agonist increased the activity in 19 neurons and decreased it in 105 neurons. On the other hand, the D2 agonist increased the activity in 54 neurons and decreased it in 50 neurons. The D1 and D2 substances modulated the activity in both Go and Nogo trials. Each of the three D1/D2 groups (D1, D2, and D1D2 groups) contained all four Go/Nogo types (Go, Nogo, Both, and Different types) of neurons. Percentages of each Go/Nogo type of neuron were comparable among the three D1/D2 groups. The D1 and D2 substances modulated the activity related to various task periods. Each of the three D1/D2 groups included neurons activated during the cue, delay, response, or reward period in Go and Nogo trials. Distributions of the neurons related to each task period were similar among the D1/D2 groups. These results suggest that dopamine can modulate the activity of single putaminal neurons through both D1 and D2 receptors and that the dopaminergic modulation through the two receptors in the putamen affects similar types of signals in behavioral control.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Biomedical Chromatography 2 (1987), S. 271-273 
    ISSN: 0269-3879
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The application of micro HPLC to the determination of amygdalin in Semen pruni armeniacae and Semen pruni persicae is described. Amygdalin is separated at ambient temperature on a reversed phase column of U-Finepak SIL C18(150×0.5 mm) with methanol + water (25: 75 v/v) as the mobile phase at a flow rate of 10 μL/min. The results are calculated by the internal standard method. The linear range is 1-7 μg. The CV and recovery of pure amygdalin are 1.47% (n = 10) and 98.13%, respectively. The results of analysis are lower than those obtained by TLC, but microHPLC is much simpler, faster, and more sensitive and reproducible than TLC.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Publication Date: 2018-02-10
    Description: Author(s): Lei Li, Jian Zou, Hai Li, Bao-Ming Xu, Yuan-Mei Wang, and Bin Shao We investigate the heat transport between two nonthermal reservoirs based on a microscopic collision model. We consider a bipartite system consisting of two identical subsystems, and each subsystem interacts with its own local reservoir, which consists of a large collection of initially uncorrelated... [Phys. Rev. E 97, 022111] Published Fri Feb 09, 2018
    Keywords: Statistical Physics
    Print ISSN: 1539-3755
    Electronic ISSN: 1550-2376
    Topics: Physics
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  • 7
    Publication Date: 2017-06-16
    Description: The purpose of this meta-analysis was to comprehensively investigate the correlation between high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) in relation to acute pancreatitis. A highly regulated exploration of various electronic databases, supplemented by manual searching methods, was performed in an attempt to identify pertinent articles of a useful nature. Subsequently, high-quality cohort studies that were deemed to comply with the arduous inclusion and exclusion criteria were selected for our meta-analysis. The extensive data analyses reported in our meta-analysis were conducted in connection with the Comprehensive Meta-analysis 2.0 (CMA 2.0). A total of 395 studies (135 Chinese studies and 260 English studies) were initially retrieved. 27 of those studies were selected for our meta-analysis, comprising of 896 cases of mild acute pancreatitis (MAP), 700 cases of severe acute pancreatitis (SAP) as well as 312 healthy controls. Pooled data suggested that serum HMGB1 and IL-6 levels of SAP and MAP patients were higher than in healthy controls. Moreover, serum HMGB1 and IL-6 levels of SAP patients exhibited significantly higher levels than in that of MAP patients. Based on the rigorous investigation of our meta-analysis, it was concluded that serum HMGB1 and IL-6 levels might be used as effective indicators for pancreatic lesions as well as the degree of inflammatory response, owing ultimately to the observations and data analyses, suggesting that serum HMGB1 and IL-6 levels share a close correlation with the severity of pancreatitis. This article is protected by copyright. All rights reserved
    Electronic ISSN: 0091-7419
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Published by Wiley-Blackwell
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