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Creatine is a crucial metabolite that plays a fundamental role in ATP homeostasis in tissues with high-energy demands. The creatine transporter (CreaT, SLC6A8) belongs to the solute carrier 6 (SLC6) transporters family, and more particularly to the GABA transporters (GATs) subfamily. Understanding the molecular determinants of specificity within the SLC6 transporters in general, and the GATs in particular is very challenging due to the high similarity of these proteins. In the study presented here, our efforts focused on finding key structural features involved in binding selectivity for CreaT using structure-based computational methods. Due to the lack of three-dimensional structures of SLC6A8, our approach was based on the realization of two reliable homology models of CreaT using the structures of two templates, i.e. the human serotonin transporter (hSERT) and the prokaryotic leucine transporter (LeuT). Our models reveal that an optimal complementarity between the shape of the binding site and the size of the ligands is necessary for transport. These findings provide a framework for a deeper understanding of substrate selectivity of the SLC6 family and other LeuT fold transporters.

Objective: This study aimed to evaluate the moment-to-moment auditory control of voice at an early stage after implantation with Clarion cochlear implants., Study Design: A perceptive and electroacoustic evaluation of the voice was carried out through a digital analysis immediately after the activation of the implant, before the fitting procedure has begun., Setting: The study was performed at the Department of Otolaryngology, University "La Sapienza" of Rome., Patients: Nine profoundly deaf subjects (five post-linguistic deaf adults, two pre-linguistic deaf children and two peri-linguistic deaf subjects, one adult and one child)., Intervention: Surgical insertion of a Clarion cochlear device., Main Outcome Measures: Qualitative (short-term pitch and energy perturbation, intonation, vocal attack, quality, and intensity) and quantitative (F0, F1, F2 and F3 frequency values), under non activated (NAI) and activated (AI) condition, have been obtained., Results: In the majority of patients, the perceptive evaluation under AI showed a lowering of voice intonation, a better control of voice intensity, and a reduction of nasal quality. These findings were confirmed by a significant lowering of F0 (Wicoxon non parametric test) in all cases and lowering of F1 and F2 in five cases. Additionally, a better definition of all formats in the majority of cases as well as by a parallelism of pitch and energy profile was observed., Conclusions: The Clarion cochlear implant device provided a recognizable moment-to-moment auditory control on voice and articulatory patterns. By monitoring the articulated voice during adjustment of the electrical stimulation at the first fitting session, one may be able to include these data and assist in the selection of the best rehabilitative strategy.