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Background-Cardiac hypertrophy is characterized by transcriptional reprogramming of fetal gene expression, and histone deacetylases (HDACs) are tightly linked to the regulation of those genes. We previously demonstrated that activation of HDAC2, 1 of the class I HDACs, mediates hypertrophy. Here, we show that casein kinase-2␣1 (CK2␣1)-dependent phosphorylation of HDAC2 S394 is required for the development of cardiac hypertrophy. Methods and Results-Hypertrophic stimuli phosphorylated HDAC2 S394, which was necessary for its enzymatic activation, and therefore the development of hypertrophic phenotypes in rat neonatal cardiomyocytes or in isoproterenoladministered mice hearts. Transgenic mice overexpressing HDAC2 wild type exhibited cardiac hypertrophy, whereas those expressing phosphorylation-resistant HDAC2 S394A did not. Compared with that in age-matched normal human hearts, phosphorylation of HDAC2 S394 was dramatically increased in patients with hypertrophic cardiomyopathy. Hypertrophy-induced phosphorylation of HDAC2 S394 and its enzymatic activity were completely blocked either by CK2 blockers or by CK2␣1 short interfering RNA. Hypertrophic stimuli led CK2␣1 to be activated, and its chemical inhibitors blocked hypertrophy in both phenylephrine-treated cardiomyocytes and isoproterenol-administered mice. CK2␣1-transgenic mice developed hypertrophy, which was attenuated by administration of trichostatin A, an HDAC inhibitor. Overexpression of CK2␣1 caused hypertrophy in cardiomyocytes, whereas chemical inhibitors of both CK2 and HDAC as well as HDAC2 S394A blunted it. Hypertrophy in CK2␣1-transgenic mice was exaggerated by crossing these mice with wild-type-HDAC2-overexpressing mice. By contrast, however, it was blocked when CK2␣1-transgenic mice were crossed with HDAC2 S394A-transgenic mice. Conclusions-We have demonstrated a novel mechanism in the development of cardiac hypertrophy by which CK2 activates HDAC2 via phosphorylating HDAC2 S394. (Circulation. 2011;123:2392-2403.)Key Words: hypertrophy Ⅲ casein kinase 2 Ⅲ histone deacetylase 2 S394 Ⅲ phosphorylation Ⅲ transgenic mice C ardiac hypertrophy, an increase in the size of cardiomyocytes, is often caused by diverse pathological conditions such as myocardial infarction, hypertension, aortic stenosis, and valvular dysfunction. Although cardiac hypertrophy itself is an initial adaptive process, uncorrected continuous stimuli often lead the heart to heart failure. Because heart failure is a main cause of human mortality, many researchers are eager to develop interventions to reverse cardiac hypertrophy or to prevent the transition to congestive heart failure. Editorial see p 2341 Clinical Perspective on p 2403Posttranslational modifications of histones are closely involved in diverse biological processes through the regulation of transcription of downstream target genes. 1,2 Among these modifications, the acetylation status of the chromatin mediates the epigenetic regulation of gene expression. Two opposing groups of enzymes, histone acetyltransferase and hi...

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Metal ion dissolution from high-capacity LiNi0.8Co0.16Al0.04normalO2 cathode material during storage at 90°C was completely blocked by a lithium-reactive Co3(PO4)2 nanoparticle coating. As opposed to conventional coating methods, in which the coating material did not react with LiOH and Li2CO3 impurities dissolved from the cathode, the Co3(PO4)2 coating material reacted with such impurities during annealing to form an olivine LiCoPO4 phase on the bulk surface. Electrochemical properties of the optimized sample, annealed at 700°C for 5h , demonstrated a 30% enhancement of the cycle life, compared to a bare sample without a loss in the first discharge capacity. Storage tests of the 4.3V charged electrode at 90°C after 7 days showed that the bare sample was transformed into the spinel phase with a Fd3m space group, whereas the Co3(PO4)2 -coated sample remained as a layered hexagonal phase with an R3false¯m space group.

BackgroundPersonal health record (PHR)–based health care management systems can improve patient engagement and data-driven medical diagnosis in a clinical setting.ObjectiveThe purpose of this study was (1) to demonstrate the development of an electronic health record (EHR)–tethered PHR app named MyHealthKeeper, which can retrieve data from a wearable device and deliver these data to a hospital EHR system, and (2) to study the effectiveness of a PHR data-driven clinical intervention with clinical trial results.MethodsTo improve the conventional EHR-tethered PHR, we ascertained clinicians’ unmet needs regarding PHR functionality and the data frequently used in the field through a cocreation workshop. We incorporated the requirements into the system design and architecture of the MyHealthKeeper PHR module. We constructed the app and validated the effectiveness of the PHR module by conducting a 4-week clinical trial. We used a commercially available activity tracker (Misfit) to collect individual physical activity data, and developed the MyHealthKeeper mobile phone app to record participants’ patterns of daily food intake and activity logs. We randomly assigned 80 participants to either the PHR-based intervention group (n=51) or the control group (n=29). All of the study participants completed a paper-based survey, a laboratory test, a physical examination, and an opinion interview. During the 4-week study period, we collected health-related mobile data, and study participants visited the outpatient clinic twice and received PHR-based clinical diagnosis and recommendations.ResultsA total of 68 participants (44 in the intervention group and 24 in the control group) completed the study. The PHR intervention group showed significantly higher weight loss than the control group (mean 1.4 kg, 95% CI 0.9-1.9; P<.001) at the final week (week 4). In addition, triglyceride levels were significantly lower by the end of the study period (mean 2.59 mmol/L, 95% CI 17.6-75.8; P=.002).ConclusionsWe developed an innovative EHR-tethered PHR system that allowed clinicians and patients to share lifelog data. This study shows the effectiveness of a patient-managed and clinician-guided health tracker system and its potential to improve patient clinical profiles.Trial RegistrationClinicalTrials.gov NCT03200119; https://clinicaltrials.gov/ct2/show/NCT03200119 (Archived by WebCite at http://www.webcitation.org/6v01HaCdd)

Using its technological capabilities, Facebook has introduced customized and more relevant commercial messages for its growing number of advertisement-savvy users. We empirically examined the factors that influence the way in which users respond to Facebook-based advertising, using the perceived advertising values posited by Ducoffe's model and Facebook usage behavior as a basis. The results of an online survey that involved 758 participants show that users are more likely to click on Facebook-based advertising if they perceive it as informative rather than irritating. Moreover, the extent to which users depend on Facebook and participate as "fans" on brand pages positively impacts the likelihood that they will click on advertising.

This study illustrates the acceptance behaviour of ubiquitous personal robot services in Korea on the basis of the previous researches on service quality, systems quality, and technology adoption. We especially build the dimensions of service quality fit for personal robot service characteristics, i.e. tangible quality and motion quality. 490 respondents collected from surveys of Korean households, who used the personal robot in their home for 4 months before the survey, were used to verify the research model. The findings reveal that perceived usefulness and user satisfaction significantly positively impact intention to use a personal robot service. Additionally, perceived usefulness has a far more significant effect on the intention to use the service than does user satisfaction. The service quality was determined to be a significant antecedent of both perceived usefulness and user satisfaction. The most influential factor was the motion quality of the ubiquitous personal robot, followed by tangible quality. System quality proved to be a major determinant of perceived usefulness and user satisfaction, and to have strong effect on perceived usefulness than service quality.