Molecular mechanisms of G protein-coupled receptor desensitization and resensitization

Beta-arrestin proteins play a dual role in regulating G protein-coupled receptor (GPCR) responsiveness by contributing to both receptor desensitization and internalization. Recently, beta-arrestins were also shown to be critical determinants for beta2-adrenergic receptor (beta2AR) resensitization. This was demonstrated by overexpressing wild-type beta-arrestins to rescue the resensitization-defect of a beta2AR (Y326A) mutant (gain of function) and overexpressing a dominant-negative beta-arrestin inhibitor of beta2AR sequestration to impair beta2AR dephosphorylation and resensitization (loss of function). Moreover, the ability of the beta2AR to resensitize in different cell types was shown to be dependent upon beta-arrestin expression levels. To further study the mechanisms underlying beta-arrestin function, green fluorescent protein was coupled to beta-arrestin2 (beta arr2GFP), thus allowing the real-time visualization of the agonist-dependent trafficking of beta-arrestin in living cells. Beta arr2GFP translocation from the cytoplasm to the plasma membrane proceeded with a time course, sensitivity and specificity that was indistinguishable from the most sensitive second messenger readout systems. Beta arr2GFP translocation was GRK-dependent and was demonstrated for 16 different ligand-activated GPCRs. Because beta-arrestin binding is a common divergent step in GPCR signalling, this assay represents a universal methodology for screening orphan receptors, GRK inhibitors and novel GPCR ligands. Moreover, beta arr2GFP provides a valuable new tool to dissect the biological function and regulation of beta-arrestin proteins.     

Pervasiveness of the relationship between intrinsic-extrinsic needs and persistence at work.

Administered inventories of 7-19 intrinsic and 8-17 extrinsic needs to 209 teachers, 25 laboratory workers, 27 psychiatric team workers, 86 building workers, 67 special education teachers, 68 nurses, and 141 youth counselors (N = 623). While persistence at work was positively correlated with intrinsic needs, no correlation was found with extrinsic needs. Results are generally consistent across populations. Data are compared with a previous study of nurses, dentists, policewomen, social workers, and youth counselors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential perception of counselor behavior.

Investigated questions raised by previous research by A. Barak and M. B. LaCrosse (1975) regarding perceptions of counselor behavior. 127 undergraduates in 3 groups viewed a film of interviews given by Ellis, Perls, or Rogers and rated them on 36 bipolar items (Counselor Rating Form). Results indicate that the perceived dimensions of expertness, attractiveness, and trustworthiness were reliable as measured by the Counselor Rating Form and were moderately intercorrelated. Significant between- and within-counselor differences were found. Results are discussed in terms of perceived counselor behavior, and questions are raised concerning the source of individuals' perceptions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Message delay and DisCSP search algorithms

Distributed constraint satisfaction problems (DisCSPs) are composed of agents, each holding its own variables, that are connected by constraints to variables of other agents. Due to the distributed nature of the problem, message delay can have unexpected effects on the behavior of distributed search algorithms on DisCSPs. This has been recently shown in experimental studies of asynchronous backtracking algorithms (Bejar et al., Artif. Intell., 161:117–148, 2005; Silaghi and Faltings, Artif. Intell., 161:25–54, 2005). To evaluate the impact of message delay on the run of DisCSP search algorithms, a model for distributed performance measures is presented. The model counts the number of non concurrent constraints checks, to arrive at a solution, as a non concurrent measure of distributed computation. A simpler version measures distributed computation cost by the non-concurrent number of steps of computation. An algorithm for computing these distributed measures of computational effort is described. The realization of the model for measuring performance of distributed search algorithms is a simulator which includes the cost of message delays. Two families of distributed search algorithms on DisCSPs are investigated. Algorithms that run a single search process, and multiple search processes algorithms. The two families of algorithms are described and associated with existing algorithms. The performance of three representative algorithms of these two families is measured on randomly generated instances of DisCSPs with delayed messages. The delay of messages is found to have a strong negative effect on single search process algorithms, whether synchronous or asynchronous. Multi search process algorithms, on the other hand, are affected very lightly by message delay.     

Effects of dopamine D?-like and D?-like agonists in rats trained to discriminate cocaine from saline: Influence of experimental history.

Effects of D?-like and D?-like agonists were compared in rats (Rattus norvegicus) with differing levels of experience (24 or 9 mo) in a cocaine discrimination procedure (5.6 mg/kg cocaine; fixed-ratio 20 schedule of food presentation). Cocaine d-amphetamine, and D?-like agonists (quinelorane, 7-OH-DPAT) dose-dependently substituted cocaine in both groups of rats. In contrast D?-like agonists (SKF 82958, SKF 7734) substituted for cocaine only in rats with less discrimination experience. Pretreatment with D?-like agonists increased the stimulus effects of low cocaine-doses in both groups, whereas D?-like agonists produced these effects only in rats with less discrimination experience. The data suggest that the stimulus effects of cocaine overlap with those of D?-like agonists across a broader range of conditions than with those of D?-like agonists. Thus, D?-like receptors may play an especially important role in cocaine's behavioral effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychomotor stimulation by dopamine D?-like but not D?-like agonists in most mouse strains.

Many neurological and psychiatric disorders are treated with dopamine modulators. Studies in mice may reveal genetic factors underlying those disorders or responsiveness to various treatments, and species and strain differences both complicate the use of mice and provide valuable tools. We evaluated psychomotor effects of the dopamine D?-like agonist R-6-Br-APB and the dopamine D?-like agonist quinelorane using a locomotor activity procedure in 15 mouse strains (inbred 129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, outbred Swiss Webster, and CD-1) and Sprague–Dawley rats, using groups of both females and males. Both D? and D? stimulation produced hyperactivity in the rats, and surprisingly, only two mouse strains were similar in that regard (C3H/HeJ, SPRET/EiJ). In contrast, the majority of mouse strains exhibited hyperactivity only with D? stimulation, whereas D? stimulation had no effect or decreased activity. BALB substrains, A/J and FVB/NJ mice showed only decreased activity after either D? or D? stimulation. CAST/EiJ mice exhibited hyperactivity exclusively with D? stimulation. Sex differences were observed but no systematic trend emerged: For example, of the five strains in which a main factor of sex was identified for the stimulant effects of the D? agonist, responsiveness was greatest in females in three of those strains and in males in two of those strains. These results should aid in the selection of mouse strains for future studies in which D? or D? responsiveness is a necessary consideration in the experimental design. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Construction safety training using immersive virtual reality

Construction workers’ ability to identify and assess risks is acquired through training and experience and is among the key factors that determine their behaviour and thus their safety. Yet researchers have questioned the effectiveness of conventional safety training. This research tested the hypotheses that safety training in a virtual reality (VR) construction site would be feasible and more effective, in terms of workers’ learning and recall in identifying and assessing construction safety risks, than would equivalent training using conventional methods. Sixty-six subjects were provided training in construction safety and their safety knowledge was tested prior to the training, immediately afterward, and one month later. Half of the subjects received traditional classroom training with visual aids; the other half were trained using a 3D immersive VR power-wall. Significant advantage was found for VR training for stone cladding work and for cast-in-situ concrete work, but not for general site safety. VR training was more effective in terms of maintaining trainees’ attention and concentration. Training with VR was more effective over time, especially in the context of cast-in-situ concrete works. Given the need for improved training and the advantages of training using VR, incorporation of VR in construction safety training is strongly recommended.