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.
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.
Respiratory system is the main section of vocal production and singing. Breathing as an involuntary muscle movement is the most essential factor of life. Its mechanism is dependent on air moving in and out of the lungs in response to pressure differences between the lungs and the atmosphere. If the air pressure within the alveolar spaces falls below atmospheric pressure, inspiration occurs with the air entering the lungs. If the air pressure within the alveoli exceeds atmospheric pressure, expiration occurs with air blown out of the lungs. During normal breathing, inspiration occurs as the diaphragm muscle contracts downward, increasing the thoracic cavity. The external intercostal muscles contract, too, expanding the rib cage. Normal breathing expiration occurs passively, while diaphragm and intercostal muscles relax. Forced breathing can occur during exercise or during actions which need active manipulation of breathing, such as singing. In forced breathing, both inspiration and expiration are done actively via contraction of the breathing muscles. In general, breathing patterns may change according to the physical activity, emotional conditions as well as health situation. In this paper, respiratory system and breathing mechanisms are explained, and studies involving the relationship between breath and singing are investigated and analyzed. According to the results, efficient larynx productivity via phonation requires a correct posture and efficient breathing. These factors also reduce tension in the vocal tract and help to provide good resonance. The singer needs to control the sounds she/he produces as well as a qualified breath support. The coordination of the singing muscles should be applied with the guidance of a good singing teacher or a professional of breathing techniques. Singing therapies had good results on patients with respiratory diseases. They developed better breathing control mechanisms and physical functioning via singing exercises. The professionals may provide different imageries according to the age and the condition of the singer/patient. During breath management teaching, constant flow of air concept may be suggested instead of using the support concept in order to decrease the tension and stress on the muscles. Further studies are recommended with longer periods of breathing and singing lessons at private sessions for better evaluations.
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