The plant hormone auxin is a master regulator of plant growth and development. By regulating rates of cell division and elongation and triggering specific patterning events, indole 3-acetic acid (IAA) regulates almost every aspect of plant development. The perception of auxin involves the formation of a ternary complex consisting of an F-box protein of the TIR1/AFB family of auxin receptors, the auxin molecule, and a member the Aux/IAA family of co-repressor proteins. In this study, we identified a potent auxin antagonist, α-(phenylethyl-2-oxo)-IAA, as a lead compound for TIR1/AFB receptors by in silico virtual screening. This molecule was used as the basis for the development of a more potent TIR1 antagonist, auxinole (α-[2,4-dimethylphenylethyl-2-oxo]-IAA), using a structure-based drug design approach. Auxinole binds TIR1 to block the formation of the TIR1-IAA-Aux/IAA complex and so inhibits auxin-responsive gene expression. Molecular docking analysis indicates that the phenyl ring in auxinole would strongly interact with Phe82 of TIR1, a residue that is crucial for Aux/IAA recognition. Consistent with this predicted mode of action, auxinole competitively inhibits various auxin responses in planta. Additionally, auxinole blocks auxin responses of the moss Physcomitrella patens, suggesting activity over a broad range of species. Our works not only substantiates the utility of chemical tools for plant biology but also demonstrates a new class of small molecule inhibitor of protein-protein interactions common to mechanisms of perception of other plant hormones, such as jasmonate, gibberellin, and abscisic acid.

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OBJECTIVENearly one-half of diabetic patients have glycated hemoglobin A1c (HbA1c) levels above recommended targets. Effective physician–patient communication improves glycemia and diabetes self-care; however, communication gaps may exist that prevent patients from discussing self-care problems with treatment providers.RESEARCH DESIGN AND METHODSWe assessed diabetic patients’ (n = 316, 85% white, 51% female, 71% type 2 diabetes, 59 ± 11 years old, 16 ± 3 years education, 19 ± 13 years diabetes duration, and HbA1c = 7.9 ± 1.4%) HbA1c, frequency of self-care, diabetes-related distress, depressive and anxiety symptoms, coping styles, diabetes quality of life, and self-care communication in the treatment relationship. Multivariate logistic regression models examined the main and interaction effects of health and psychosocial factors associated with patients’ reluctance to discuss self-care.RESULTSPatients reported positive relationships with their doctors and valued honest communication; however, 30% of patients were reluctant to discuss self-care. Reluctant patients reported less frequent self-care (P = 0.05), lower diabetes quality of life (P = 0.002), and more diabetes-related distress (P = 0.001), depressive symptoms (P < 0.001), and anxiety symptoms (P = 0.001). Patients who reported elevated depressive symptoms, although not necessarily major depression, were more likely to be reluctant to discuss self-care (odds ratio [OR] 1.66 for 10-point change in t score; P < 0.001), whereas patients who were older (OR 0.78 for 10-year change; P = 0.05) and those who used more self-controlled coping styles (OR 0.78 for 10-point change; P = 0.007) were less likely to be reluctant.CONCLUSIONSAwareness of elevated depressive symptoms is important in clinical practice given that these patients may be more reluctant to discuss self-care. Interventions and evidence-based approaches are needed to improve both depressive symptoms and physician-patient communication about self-care.

Ensuring quality of life (QOL) while maintaining glycemic control within targets is an important challenge in type 1 and type 2 diabetes treatment. For children with diabetes, QOL includes enjoying meals, feeling safe in school, and perceiving positive, supportive relationships with parents, siblings, and friends. Yet many treatment-related and psychosocial barriers can interfere with a child’s QOL and their ability to manage diabetes effectively. Diabetes management also imposes considerable lifestyle demands that are difficult and often frustrating for children to negotiate at a young age. Recent advances in diabetes medications and technologies have improved glycemic control in children with diabetes. Two widely used technologies are the insulin pump and continuous glucose monitoring (CGM) system. These technologies provide patients with more flexibility in their daily life and information about glucose fluctuations. Several studies report improvements in glycemic control in children with type 1 diabetes using the insulin pump or sensor-augmented pump therapy. Importantly, these technologies may impact QOL for children and families with diabetes, although they are rarely used or studied in the treatment of children with type 2 diabetes. Further, emerging closed loop and web- and phone-based technologies have great potential for supporting diabetes self-management and perhaps QOL. A deeper understanding and appreciation of the impact of diabetes technology on children’s and parents’ QOL is critical for both the medical and psychological care of diabetes. Thus, the purpose of this review is to discuss the impact of new diabetes technologies on QOL in children, adolescents and families with type 1 diabetes.