Tongue retraining and occlusal stability in a young adult. Case report

The clinical observation describes the case of a 20-year-old woman who has consulted for aesthetic and functional reasons. She presents a skeletal class III normodivergent, an occlusal class III with a lower proalveoli quite marked. In addition, a lingual dysfunction which manifests itself by important anterior diastema and dento-dental disharmony at the upper jaw complicates the case. The undertaken therapeutic project starts with a first step of a lingual praxis rehabilitation, followed by an orthodontic step and upper lateral incisors-plasty. The purpose of those results is the evaluation of the stability two years later, which was reported positive.     

3D variable‐density SPARKLING trajectories for high‐resolution T2*‐weighted magnetic resonance imaging

We have recently proposed a new optimization algorithm called SPARKLING (Spreading Projection Algorithm for Rapid K‐space sampLING) to design efficient compressive sampling patterns for magnetic resonance imaging (MRI). This method has a few advantages over conventional non‐Cartesian trajectories such as radial lines or spirals: i) it allows to sample the k‐space along any arbitrary density while the other two are restricted to radial densities and ii) it optimizes the gradient waveforms for a given readout time. Here, we introduce an extension of the SPARKLING method for 3D imaging by considering both stacks‐of‐SPARKLING and fully 3D SPARKLING trajectories. Our method allowed to achieve an isotropic resolution of 600 μm in just 45 seconds for T2? ‐weighted ex vivo brain imaging at 7 Tesla over a field‐of‐view of 200 × 200 × 140 mm³ . Preliminary in vivo human brain data shows that a stack‐of‐SPARKLING is less subject to off‐resonance artifacts than a stack‐of‐spirals.     

Insights into the cholecystokinin 2 receptor binding site and processes of activation

The cholecystokinin (CCK) 2 receptor (CCK2R) appears as a pharmacological target for the treatment of many major diseases. To complete the mapping of the CCK2R binding site and its activation processes, we have looked for the receptor residues that interact with Trp6, an essential residue for CCK binding and activity. In our molecular model of the CCK-occupied CCK2R, the indole group of Trp6 stacked with the phenyl ring of Phe120 (ECL1) and interacted with the imidazole group of His381(H7.39) and the phenyl ring of Tyr385(H7.43). Mutagenesis and pharmacological studies validated these interactions. It is noteworthy that the mutation of Phe120 to Trp conferred constitutive activity to the CCK2R. Molecular modeling and experimental works identified the residues involved in the activation cascade initiated by Trp6 and revealed that the constitutively active F120W mutation mimics the conformational changes induced by Trp6 resulting in: 1) the exposure of Glu151(E3.49) of the conserved E/DRY motif 2) the formation of an amphiphatic pocket involving protonated Glu151(E3.49) and Leu330 (ICL3), and 3) the opening of the intracellular loops 2 and 3 and the release of Arg158 (ICL2). The R158A mutation was shown to affect inositol phosphate production, whereas the E151A and L330E mutations induced constitutive inositol phosphate production. Given that a constitutively active variant of the CCK2R has been identified in different cancers and the fact that the E151A mutant has been reported to induce tumors, these studies should help in the development of potent inverse agonists to inhibit the constitutive activation of the CCK2R.