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.

No abstract

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.

Background & AimsThe utility of transient elastography (FibroScan) is well studied in adults but not in children. We sought to assess the feasibility of performing FibroScans and the characteristics of FibroScan-based liver profiles in Japanese obese and non-obese children.MethodsFibroScan examinations were performed in pediatric patients (age, 1–18 yr) who visited Osaka City University Hospital. Liver steatosis measured by controlled attenuation parameter (CAP), and hepatic fibrosis evaluated as the liver stiffness measurement (LSM), were compared among obese subjects (BMI percentile ≥90%), non-obese healthy controls, and non-obese patients with liver disease.ResultsAmong 214 children examined, FibroScans were performed successfully in 201 children (93.9%; median, 11.5 yr; range, 1.3–17.6 yr; 115 male). CAP values (mean±SD) were higher in the obese group (n = 52, 285±60 dB/m) compared with the liver disease (n = 40, 202±62, P<0.001) and the control (n = 107, 179±41, P<0.001) group. LSM values were significantly higher in the obese group (5.5±2.3 kPa) than in the control (3.9±0.9, P<0.001), but there were no significant differences in LSM between the liver disease group (5.4±4.2) and either the obese or control group. LSM was highly correlated with CAP in the obese group (ρ = 0.511) but not in the control (ρ = 0.129) or liver disease (ρ = 0.170) groups.ConclusionsChildhood obesity carries a high risk of hepatic steatosis associated with increased liver stiffness. FibroScan methodology provides simultaneous determination of CAP and LSM, is feasible in children of any age, and is a non-invasive and effective screening method for hepatic steatosis and liver fibrosis in Japanese obese children.

Polar auxin movement is a primary regulator of programmed and plastic plant development. Auxin transport is highly regulated at the cellular level and is mediated by coordinated transport activity of plasma membrane-localized PIN, ABCB, and AUX1/LAX transporters. The activity of these transporters has been extensively analyzed using a combination of pharmacological inhibitors, synthetic auxins, and knock-out mutants in Arabidopsis. However, efforts to analyze auxin-dependent growth in other species that are less tractable to genetic manipulation require more selective inhibitors than are currently available. In this report, we characterize the inhibitory activity of 5-alkoxy derivatives of indole 3-acetic acid and 7-alkoxy derivatives of naphthalene 1-acetic acid, finding that the hexyloxy and benzyloxy derivatives act as potent inhibitors of auxin action in plants. These alkoxy-auxin analogs inhibit polar auxin transport and tropic responses associated with asymmetric auxin distribution in Arabidopsis and maize. The alkoxy-auxin analogs inhibit auxin transport mediated by AUX1, PIN, and ABCB proteins expressed in yeast. However, these analogs did not inhibit or activate SCF TIR1 auxin signaling and had no effect on the subcellular trafficking of PIN proteins. Together these results indicate that alkoxy-auxins are inactive auxin analogs for auxin signaling, but are recognized by PIN, ABCB, and AUX1 auxin transport proteins. Alkoxyauxins are powerful new tools for analyses of auxin-dependent development.

Massive stars in a certain mass range may form low-mass black holes after supernova explosions. In such massive stars, fallback of D0.1 materials onto a black hole is expected because of a deep gravi-M _ tational potential or a reverse shock propagating back from the outer composition interface. We study hydrodynamical disk accretion onto a newborn low-mass black hole in a supernova using the smoothed particle hydrodynamics method. If the progenitor was rotating before the explosion, the fallback material should have a certain amount of angular momentum with respect to the black hole, thus forming an accretion disk. The disk material will eventually accrete toward the central object because of viscosity at a supercritical accretion rate, for the Ðrst several tens of days. (Here, is the Edding-M 0 /M 0 crit [ 106, M 0 crit ton luminosity divided by c2.) We then expect that such an accretion disk is optically thick and advection dominated ; that is, the disk is so hot that the produced energy and photons are advected inward rather than being radiated away. Thus, the disk luminosity is much less than the Eddington luminosity. The disk becomes hot and dense ; for for example,being the viscosity parameter) in the vicinity of the black hole. Depend-103(a vis /0.01)~1 a vis ing on the material mixing, some interesting nucleosynthesis processes via rapid proton and alphaparticle captures are expected even for reasonable viscosity magnitudes and some of them (a vis D 0.01), could be ejected in a disk wind or a jet without being swallowed by the black hole.

Abstract.The objective of this study was to identify factors affecting on errors in carbohydrate (CHO) content estimation during CHO counting. Thirty-seven type 1 diabetes patients and 22 of their parents and 28 physicians/dieticians were enrolled in this study. CHO counting was counted in “Carb”, with 1 Carb defined as 10 g of CHO. To evaluate the accuracy of CHO counting, 80 real-size photographs of cooked meals were presented to the subjects for Carb estimation. Carbs tended to be overestimated for foods containing relatively small amounts of Carbs. On the other hands, Carbs tended to be underestimated for foods with higher than 6 Carbs. Accurate estimation of the Carbs in food containing a large amount of rice was particularly difficult even in the subjects having the CHO counting experience. The Carb contents of high-calorie foods such as meats, fried foods, and desserts tended to be overestimated. This error was smaller in subjects having the CHO counting experience. In conclusion, misunderstanding of high-calorie dishes containing high amounts of CHO was observed in inexperienced subjects, indicating the efficacy of the current methodology of CHO counting. On the other hand it was difficult even for experienced subjects to assess the amount of seasoned rice, suggesting the need for a new methodology for accurate estimation.