Arrestins selectively bind to phosphorylated activated forms of their cognate G protein-coupled receptors. Arrestin binding prevents further G protein activation and often redirects signaling to other pathways. The comparison of the high-resolution crystal structures of arrestin2, visual arrestin, and rhodopsin as well as earlier mutagenesis and peptide inhibition data collectively suggest that the elements on the concave sides of both arrestin domains most likely participate in receptor binding directly, thereby dictating its receptor preference. Using comparative binding of visual arrestin/arrestin2 chimeras to the preferred target of visual arrestin, light-activated phosphorylated rhodopsin (PRh^*), and to the arrestin2 target, phosphorylated activated m2 muscarinic receptor (P-m2 mAChR^*), we identified the elements that determine the receptor specificity of arrestins. We found that residues 49–90 (β-strands V and VI and adjacent loops in the N-domain) and 237–268 (β-strands XV and XVI in the C-domain) in visual arrestin and homologous regions in arrestin2 are largely responsible for their receptor preference. Only 35 amino acids (22 of which are nonconservative substitutions) in the two elements are different. Simultaneous exchange of both elements between visual arrestin and arrestin2 fully reverses their receptor specificity, demonstrating that these two elements in the two domains of arrestin are necessary and sufficient to determine their preferred receptor targets.

Objective: To characterize the soft tissue features of infants with unilateral cleft lip (UCL) and unilateral complete cleft lip and palate (UCLP) prior to primary surgery and compare with noncleft controls. Design: Prospective controlled capture of the facial morphology of infants using a noninvasive three-dimensional stereophotogrammetry method. Participants: 23 children with presurgical cleft: 11 UCL (M = 6, F = 5); 12 UCLP (M = 9, F = 3), and 21 noncleft controls (M = 7, F = 14) were imaged at approximately 3 months of age (range 10 to 16 weeks). Main Outcome Measure: Accurate, repeatable quantification of facial soft tissues in infants with clefts prior to surgery. Results: Significant differences (p < .05) were found between the UCLP group and UCL and control groups in anatomical and soft nose width, cleft-side alar wing length, and nasal tip horizontal displacement. Both cleft groups were significantly different from controls and from each other in cleft-side nostril dimensions, alar wing angulation, columella angle, and alar base to corner of mouth dimension; alar base width; and soft tissue defect in nose and the lip and philtrum length bordering the cleft. Significant differences between clefts and controls were identified in the nostril and philtrum on the noncleft side. Conclusions: The use of children with UCL as controls for UCLP studies is inappropriate. This technique overcame the limitations of direct measurement of infant faces to aid the surgeon in the planning and subsequent re-evaluation of surgical rationale.

Despite overall improvements in oral health, a large number of children in United Kingdom (UK) are affected by dental caries; and the implementation of oral health promotion in some families remains a challenge. As such, children from those families suffer high caries rates, and are frequently referred for tooth extraction under General Anaesthesia (GA), one of the commonest reasons for paediatric hospital admissions. The aim of this investigation is to explore referring primary care General Dental Practitioners’ (GDPs) views and experiences in trying to promote better oral health for those children. A qualitative study, utilizing face-to-face, semi-structured interviews with GDPs in three London boroughs who refer children for extraction of decayed teeth under GA selected based on referral rate. Qualitative Framework Analysis was used to present the results. Eighteen GDPs (56% male) were interviewed: average age 42 years (range: 26–73 years). informants reported challenges to promotion of oral health categorised as: (1) child’s young age, poor cooperation, and high treatment need; (2) parental skills to face up to modern day challenges and poor attitudes towards good oral health (3); social inequality, exclusion and cultural barriers in immigrant families; (4) National Health Services (NHS) primary care practice remuneration, constraints and training; (5) inadequate secondary care communication and engagement; and (6) failure in establishing national policy to grasp the width and depth of the problem. GDPs feel frustrated and isolated in their efforts to promote oral health in those children. These findings suggest difficult challenges on all fronts. Reform of preventive dentistry funding and delivery, as well as a multiagency multidimensional approach that is mindful of the social determinants of children’s oral health and barriers to application of oral and wider health initiatives are needed to address this important public health issue.