BackgroundThis study investigates the allosteric coupling that exists between the intra- and extracellular parts of human β2-adrenergic receptor (β2-AR), in the presence of the intracellular loop 3 (ICL3), which is missing in all crystallographic experiments and most of the simulation studies reported so far. Our recent 1 μs long MD run has revealed a transition to the so-called very inactive state of the receptor, in which ICL3 packed under the G protein’s binding cavity and completely blocked its accessibility to G protein. Simultaneously, an outward tilt of transmembrane helix 5 (TM5) caused an expansion of the extracellular ligand-binding site. In the current study, we performed independent runs with a total duration of 4 μs to further investigate the very inactive state with packed ICL3 and the allosteric coupling event (three unrestrained runs and five runs with bond restraints at the ligand-binding site).ResultsIn all three independent unrestrained runs (each 500 ns long), ICL3 preserved its initially packed/closed conformation within the studied time frame, suggesting an inhibition of the receptor’s activity. Specific bond restraints were later imposed between some key residues at the ligand-binding site, which have been experimentally determined to interact with the ligand. Restraining the binding site region to an open state facilitated ICL3 closure, whereas a relatively constrained/closed binding site hindered ICL3 packing. However, the reverse operation, i.e. opening of the packed ICL3, could not be realized by restraining the binding site region to a closed state. Thus, any attempt failed to free the ICL3 from its locked state due to the presence of persistent hydrogen bonds.ConclusionsOverall, our simulations indicated that starting with very inactive states, the receptor stayed almost irreversibly inhibited, which in turn decreased the overall mobility of the receptor. Bond restraints which represented the geometric restrictions caused by ligands of various sizes when bound at the ligand-binding site, induced the expected conformational changes in TM5, TM6 and consequently, ICL3. Still, once ICL3 was packed, the allosteric coupling became ineffective due to strong hydrogen bonds connecting ICL3 to the core of the receptor.Electronic supplementary materialThe online version of this article (doi:10.1186/s12900-016-0061-9) contains supplementary material, which is available to authorized users.

The novel La Dame aux Camelias written by Alexandre Dumas fils and the opera La Traviata composed by Giuseppe Verdi depict the so-called pleasurable life and tragic end of an elite courtesan, who faces true love and death. The reason of death is tuberculosis, a disease which was the most popular and romantic one, accepted to be suitable especially for sinful women as a redemption of their sins in the 19th century literature and opera. The society’s prejudices about Marguerite and Violetta’s sins are erased by the great sacrifice that the heroines do: Leaving the beloved man for their sake of dignity and honor. In this paper, the novel and the opera are compared through the plot analysis and the end of the stories of the heroines. The composer provides the characters in the opera and the audience to suffer less compared to the novel, via choosing a slightly peaceful farewell for Violetta. The author could express the psychological dimensions of being a fallen woman and the sacrifice made more profoundly, since he could use the power of words more freely than the composer. However, the composer could mesmerize the audience via the potential of musical and theatrical elements, thus ensured the work to be one of the legends of the opera world. In any circumstances, both the art works lead the audience and the reader to ask questions about the true nature of dignity, purity and love. They expose the courtesans’ need for compassion, sympathy and tenderness to a higher class society who are prone to think that courtesans are low by class. The success behind this story is making the society face its prejudices through the dramatical death of a fallen woman.

No abstract

Musicians usually complain about stress, musculoskeletal disorders and performance anxiety during music performances. Alexander Technique is a psychophysical method which releases unwanted muscle tension, inhibits unnecessary habitual behaviors causing chronic neck and back-pain, and re-educates nonbeneficial movement patterns. This paper evaluated studies which applied the Alexander Technique to investigate its effectiveness in music students and musicians during music performances. According to the results, it was observed that performance anxiety may be decreased through the Alexander Technique sessions. In order to explore the effect of the Alexander Technique on the music performances and performance anxieties of music students and musicians to a greater extent, well-designed future studies with one-to-one lessons from experienced, professional and licensed teachers are crucial for better results.

Narcissism is defined as a personality disorder by clinical psychologists, who consider narcissists as seekers of admiration with a lack of empathy. According to social psychologists, narcissists are self-assured individuals with leadership traits and excessive interest in themselves. This study makes a literature review to find out about the beneficial and non-beneficial characteristics of narcissists, their relationships, anger management and decision making processes, as well as the reflections of these features on performing arts, which may force artists to be narcissistic. Narcissists' interpersonal relationships are generally weak and they tend to be aggressive towards criticism and negative feedback. They focus on reward and give risky decisions due to overconfidence, making them attractive and dangerous at the same time. Performers should distinguish between an inner self and a commercial self in order to eliminate the harmful effects of narcissism and to have a more peaceful and healthy performing life.