Evidence That Interspecies Polymorphism in the Human and Rat Cholecystokinin Receptor-2 Affects Structure of the Binding Site for the Endogenous Agonist Cholecystokinin

The cholecystokinin (CCK) receptor-2 exerts very important central and peripheral functions by binding the neuropeptides cholecystokinin or gastrin. Because this receptor is a potential therapeutic target, great interest has been devoted to the identification of efficient antagonists. However, interspecies genetic polymorphism that does not alter cholecystokinin-induced signaling was shown to markedly affect activity of synthetic ligands. In this context, precise structural study of the agonist binding site on the human cholecystokinin receptor-2 is a prerequisite to elucidating the molecular basis for its activation and to optimizing properties of synthetic ligands. In this study, using site-directed mutagenesis and molecular modeling, we delineated the binding site for CCK on the human cholecystokinin receptor-2 by mutating amino acids corresponding to that of the rat homolog. By doing so, we demonstrated that, although resembling that of rat homolog, the human cholecystokinin receptor-2 binding site also displays important distinct structural features that were demonstrated by susceptibility to several point mutations (F120A, Y189A, H207A). Furthermore, docking of CCK in the human and rat cholecystokinin receptor-2, followed by dynamic simulations, allowed us to propose a plausible structural explanation of the experimentally observed difference between rat and human cholecystokinin-2 receptors.

Marie Sallé, a Wise Professional Woman of Influence

This study maps the extent of Sallé's influence while identifying her self agency in moulding her image and developing her career.

Marie Sallé and the development of the ballet en action

Sallé's ballets en action are evaluated in terms of Enlightenment dramaturgical principles, and her role in shaping this aesthetic is mooted.

Marie Sallé, Handel, Rameau and the development of narrative dance music:Bericht vom Internationalen Symposium an der Hochschule fur Musik und Theater Leipzig

Paradigmatic analysis reveals that these two composers developed distinct responses to creating narrative in dance music

Marie Sallé as muse, Handel's music for mime

Considers Handel's musical response to a dancer-choreographer in line with then-current styles of dance

'Dancing at the English Opera':'Marie Salle's letter to the Duchess of Richmond

A letter from dancer Marie Salle to her patroness dated 1731 reveals her ambitions to dance at the English opera.

'Marie Salle'

This dictionary entry, which highlights the choreographer's significance to the historical study of music, is placed in a very high profile and reputable online resource.

Depicting Characters and danced Narratives: Handel, 'The Italian troupe', and Marie Sallé

Handel’s London career afforded opportunities for responding to dancers working in distinct styles of movement—most notably the Italian troupe resident at the King’s Theatre in 1726-27, and Marie Sallé at Covent Garden in 1734-35. By studying the dances from Admeto (1727) and Ariodante (1735), this paper will explore Handel's response to the serious and grotesque styles, as well as to the character and narrative modes.