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Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations. Nonetheless, the pathophysiological roles of MeCP2 mutations in the etiology of intrinsic cardiac abnormality and sudden death remain unclear. In this study, we performed a detailed functional studies (calcium and electrophysiological analysis) and RNA-sequencing-based transcriptome analysis of a pair of isogenic RTT female patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) that expressed either MeCP2wildtype or MeCP2mutant allele and iPSC-CMs from a non-affected female control. The observations were further confirmed by additional experiments, including Wnt signaling inhibitor treatment, siRNA-based gene silencing, and ion channel blockade. Compared with MeCP2wildtype and control iPSC-CMs, MeCP2mutant iPSC-CMs exhibited prolonged action potential and increased frequency of spontaneous early after polarization. RNA sequencing analysis revealed up-regulation of various Wnt family genes in MeCP2mutant iPSC-CMs. Treatment of MeCP2mutant iPSC-CMs with a Wnt inhibitor XAV939 significantly decreased the β-catenin protein level and CACN1AC expression and ameliorated their abnormal electrophysiological properties. In summary, our data provide novel insight into the contribution of activation of the Wnt/β-catenin signaling cascade to the cardiac abnormalities associated with MeCP2 mutations in RTT.

BackgroundInternational guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice.ObjectiveTo implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM).MethodA prospective screening study at the DM complication screening centre was performed.ResultsBetween 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3–5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged =0.007*), CKD (pConclusionNT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Patients infected with SARS-CoV-2 may deteriorate rapidly and therefore continuous monitoring is necessary. We conducted an observational study involving patients with mild COVID-19 to explore the potentials of wearable biosensors and machine learning-based analysis of physiology parameters to detect clinical deterioration. Thirty-four patients (median age: 32 years; male: 52.9%) with mild COVID-19 from Queen Mary Hospital were recruited. The mean National Early Warning Score 2 (NEWS2) were 0.59 ± 0.7. 1231 manual measurement of physiology parameters were performed during hospital stay (median 15 days). Physiology parameters obtained from wearable biosensors correlated well with manual measurement including pulse rate (r = 0.96, p r = 0.87, p p r = 0.75, p

BACKGROUND Prevention of heart failure (HF) has been recognized as an urgent public health need. International guidelines recommend natriuretic peptide biomarker-based screening for patients at high HF risk to allow early detection and intervention to delay HF progression and mortality. Little has been reported the incorporation of screening procedure to existing clinical practice. The objective of the study was to describe the opportunistic screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD This was a prospective screening study at the DM complication screening center. RESULTS Between 2018 and 2019, 1,132 consecutive DM patients with no prior history of HF or atrial fibrillation (AF) attending regular complication screening were invited to participate. Of these, 89 patients refused or failed to complete the screening. The final analysis included 1,043 patients (age: 63.7±12.4 years; male: 56.3%). The mean HbA1c was 7.25±1.34%. There were 81.8% patients with concomitant hypertension, 31.1% with coronary artery disease, 8.0% with previous stroke, and 5.5% with peripheral artery disease. Furthermore, 45.7% patients had diabetic retinopathy, 33.6% had peripheral neuropathy, and 30.7% had chronic kidney disease (CKD) stage 3-5. At the screening session, 43 patients (4.1%) had an elevated NT-proBNP concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected AF. The prevalence of elevated NT-proBNP concentration increased with age from 0.85% in patients aged

BackgroundA high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance.MethodsWe performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1–4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results.ResultsThe mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillation (1.0%), and newly detected left ventricular systolic dysfunction with elevated NT-proBNP level (1.0%). Significant sinus bradycardia with heart rate below 50 bpm was detected in 7.2% COVID-19 survivors, which appeared to be self-limiting and recovered over time. For COVID-19 survivors with persistent elevation of troponin level after discharge or newly detected T wave abnormality, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction.ConclusionCardiac abnormality is common amongst COVID-survivors with mild disease, which is mostly self-limiting. Nonetheless, cardiac surveillance in form of ECG and/or serum biomarkers may be advisable to detect more severe cardiac involvement including atrial fibrillation and left ventricular dysfunction.

BACKGROUND: SARS-CoV-2 infection is associated with myocardial injury, but there is a paucity of experimental platforms for the condition.Methods and Results:Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected by SARS-CoV-2 for 3 days ceased beating and exhibited cytopathogenic changes with reduced viability. Active viral replication was evidenced by an increase in supernatant SARS-CoV-2 and the presence of SARS-CoV-2 nucleocaspid protein within hiPSC-CMs. Expressions of BNP, CXCL1, CXCL2, IL-6, IL-8 and TNF-α were upregulated, while ACE2 was downregulated. CONCLUSIONS: Our hiPSC-CM-based in-vitro SARS-CoV-2 myocarditis model recapitulated the cytopathogenic effects and cytokine/chemokine response. It could be exploited as a drug screening platform.

The clinical experience gathered throughout the years has raised awareness of primary immunodeficiency diseases (PIDD). T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) assays for thymic and bone marrow outputs measurement have been widely implemented in newborn screening (NBS) programs for Severe Combined Immunodeficiency. The potential applications of combined TREC and KREC assay in PIDD diagnosis and immune reconstitution monitoring in non-neonatal patients have been suggested. Given that ethnicity, gender, and age can contribute to variations in immunity, defining the reference intervals of TREC and KREC levels in the local population is crucial for setting up cut-offs for PIDD diagnosis. In this retrospective study, 479 healthy Chinese sibling donors (240 males and 239 females; age range: 1 month-74 years) from Hong Kong were tested for TREC and KREC levels using a simultaneous quantitative real-time PCR assay. Age-specific 5th-95th percentile reference intervals of TREC and KREC levels (expressed in copies per μL blood and copies per 106 cells) were established in both pediatric and adult age groups. Significant inverse correlations between age and both TREC and KREC levels were observed in the pediatric age group. A significant higher KREC level was observed in females than males after 9-12 years of age but not for TREC. Low TREC or KREC levels were detected in patients diagnosed with mild or severe PIDD. This assay with the established local reference intervals would allow accurate diagnosis of PIDD, and potentially monitoring immune reconstitution following haematopoietic stem cell transplantation or highly active anti-retroviral therapy in the future.

Aims To recapitulate progressive human dilated cardiomyopathy (DCM) and heart block in the Lmna R225X mutant mice model and investigate the molecular basis of LMNA mutation induced cardiac conduction disorders (CD); To investigate the potential interventional impact of exercise endurance. Methods and results A Lmna R225X knock-in mice model in either heterozygous or homozygous genotype was generated. Electrical remodeling was observed with higher occurrence of AV block from neonatal and aged mutant mice as measured by surface electrocardiogram and atrio-ventricular Wenckebach point detection. Histological and molecular profiles revealed an increase in apoptotic cells and activation of caspase-3 activities in heart tissue. Upon aging, extracellular cellular matrix (ECM) remodeling appeared with accumulation of collagen in Lmna R225X mutant hearts as visualized by Masson’s trichrome stain. This could be explained by the upregulated ECM gene expression, such as Fibronectin: Fn1, collagen: Col12a1, intergrin: Itgb2 and 3, as detected by microarray gene chip. Also, endurance exercise for 3 month improved the ventricular ejection fraction, attenuated fibrosis and cardiomyocytes apoptosis in the aged mutant mice. Conclusions The mechanism of LMNA nonsense mutation induced cardiac conduction defects through AV node fibrosis is due to upregulated ECM gene expression upon activation of cardiac apoptosis. Lmna R225X mutant mice hold the potential for serving as in vivo models to explore the mechanism and therapeutic methods for AV block or myopathy associated with the aging process.

Patients with Danon disease may suffer from severe cardiomyopathy, skeletal muscle dysfunction as well as varying degrees of mental retardation, in which the primary deficiency of lysosomal membrane-associated protein-2 (LAMP2) is considerably associated. Owing to the scarcity of human neurons, the pathological role of LAMP2 deficiency in neural injury of humans remains largely elusive. However, the application of induced pluripotent stem cells (iPSCs) may shed light on overcoming such scarcity. In this study, we obtained iPSCs derived from a patient carrying a mutated LAMP2 gene that is associated with Danon disease. By differentiating such LAMP2-deficient iPSCs into cerebral cortical neurons and with the aid of various biochemical assays, we demonstrated that the LAMP2-deficient neurons are more susceptible to mild oxidative stress-induced injury. The data from MTT assay and apoptotic analysis demonstrated that there was no notable difference in cellular viability between the normal and LAMP2-deficient neurons under non-stressed condition. When exposed to mild oxidative stress (10 μM H2O2), the LAMP2-deficient neurons exhibited a significant increase in apoptosis. Surprisingly, we did not observe any aberrant accumulation of autophagic materials in the LAMP2-deficient neurons under such stress condition. Our results from cellular fractionation and inhibitor blockade experiments further revealed that oxidative stress-induced apoptosis in the LAMP2-deficient cortical neurons was caused by increased abundance of cytosolic cathepsin L. These results suggest the involvement of lysosomal membrane permeabilization in the LAMP2 deficiency associated neural injury., Highlights • We generated iPSCs from patients with LAMP2-c.183_184insA mutation. • We differentiated the patient specific iPSCs into LAMP2-deficient cortical neurons. • The LAMP2-deficient neurons are more susceptible to oxidative stress induced cell death. • Cathepsin L inhibitor rescued oxidative stress induced cell death in LAMP2-deficient neurons.

RATIONALE. Although perceived obligations to meet the expectations of family, friends, and society can be detrimental to physical health, much research in this area has thus far been conducted exclusively on Western samples. Cross-cultural research importantly suggests that positive health can be dependent on whether one engages in modes of being that are sanctioned by one’s culture. Specifically, studies show that better health is predicted when people from cultures that value independence are able to exercise their personal autonomy and when people from cultures that value interdependence are able to maintain relational harmony (Kitayama, Karasawa, Curhan, Ryff, & Markus, 2010). OBJECTIVE. Based on these lines of research, as the fulfillment of perceived obligations can facilitate relational harmony but infringe on personal autonomy, we posit that culture will moderate the impact of perceived obligations on health outcomes. To gain further insight, we additionally examined people’s goal disengagement tendency as an individual difference that may influence their likelihood of shunning perceived obligations in order to avoid associated stressors. METHOD. Drawing from the parallel biomarker projects of Midlife in the United States (MIDUS) and Midlife in Japan (MIDJA), we examined the interaction between perceived obligations and goal disengagement tendency on health among American and Japanese middle-aged adults. Health outcomes were indexed by biomarkers of inflammation (interleukin-6 and C-reactive protein levels) and cardiovascular risk (systolic blood pressure and total/high-density lipoprotein cholesterol). RESULTS. We found that a higher tendency to disengage from stressful social obligations is associated with better health for Americans. In contrast, we found poorer health outcomes amongst Japanese participants who tend to disengage from their perceived obligations. CONCLUSION. Our results highlight the importance of examining how perceived obligations influence physical health from a cultural perspective. The current study supports the hypothesis that culturally distinct pathways underlie health outcomes.

Empagliflozin, a sodium-glucose co-transporter (SGLT) inhibitor, reduces heart failure and sudden cardiac death but the underlying mechanisms remain elusive. In cardiomyocytes, SGLT1 and SGLT2 expression is upregulated in diabetes mellitus, heart failure, and myocardial infarction. We hypothesise that empagliflozin exerts direct effects on cardiomyocytes that attenuate diabetic cardiomyopathy. To test this hypothesis, cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) were used to test the potential effects of empagliflozin on neutralization of cardiac dysfunction induced by diabetic-like cultures. Our results indicated that insulin-free high glucose culture significantly increased the size of and NPPB, SGLT1 and SGLT2 expression of hiPSC-derived cardiomyocytes. In addition, high glucose-treated hiPSC-derived cardiomyocytes exhibited reduced contractility regardless of the increased calcium transient capacity. Interestingly, application of empagliflozin before or after high glucose treatment effectively reduced the high glucose-induced cardiac abnormalities. Since application of empagliflozin did not significantly alter viability or glycolytic capacity of the hiPSC-derived cardiomyocytes, it is plausible that empagliflozin exerts its effects via the down-regulation of SGLT1, SGLT2 and GLUT1 expression. These observations provide supportive evidence that may help explain its unexpected benefit observed in the EMPA-REG trial.

Background Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in the environment, lifestyle, and genetic makeup of patients. Patient‐specific human induced pluripotent stem cells hold promise to transform precision medicine into real‐life clinical practice. Lamin A/C ( LMNA )‐related cardiomyopathy is the most common inherited cardiomyopathy in which a substantial proportion of mutations in the LMNA gene are of nonsense mutation. PTC 124 induces translational read‐through over the premature stop codon and restores production of the full‐length proteins from the affected genes. In this study we generated human induced pluripotent stem cells‐derived cardiomyocytes from patients who harbored different LMNA mutations (nonsense and frameshift) to evaluate the potential therapeutic effects of PTC 124 in LMNA ‐related cardiomyopathy. Methods and Results We generated human induced pluripotent stem cells lines from 3 patients who carried distinctive mutations (R225X, Q354X, and T518fs) in the LMNA gene. The cardiomyocytes derived from these human induced pluripotent stem cells lines reproduced the pathophysiological hallmarks of LMNA ‐related cardiomyopathy. Interestingly, PTC 124 treatment increased the production of full‐length LMNA proteins in only the R225X mutant, not in other mutations. Functional evaluation experiments on the R225X mutant further demonstrated that PTC 124 treatment not only reduced nuclear blebbing and electrical stress‐induced apoptosis but also improved the excitation‐contraction coupling of the affected cardiomyocytes. Conclusions Using cardiomyocytes derived from human induced pluripotent stem cells carrying different LMNA mutations, we demonstrated that the effect of PTC 124 is codon selective. A premature stop codon UGA appeared to be most responsive to PTC 124 treatment.

Aims Recent studies suggested that the development of neuropathic pain associated with neural injury may be partly due to up-regulation of cyclooxygenase (COX) in the central nervous system. However, the cellular sources of COX-1 and COX-2 up-regulation following nerve injury are unclear. Methods We investigated the spinal cellular sources of COX-1 and COX-2 in association with allodynia following L5 spinal nerve ligation (SNL). Results Post-SNL pain-related behaviour was shown by increased sensitivity to mechanical stimulation. There was a significant increase in both COX-1 and COX-2 immunoreactivity (P

Past studies indicated that people in a minority (vs. majority) position are slower to express their public/political opinion, and the larger the difference between the size of the two positions, the slower the response. Bassili termed this the minority-slowness effect (MSE). In the current study, two experiments were conducted to demonstrate that MSE extends to people's understanding of utterances and explored the cognitive basis for this. Participants were asked to judge if an utterance is a ‘direct’ or an ‘indirect’ expression. The results show that participants in the minority (vs. majority) took longer to respond, and the larger the difference between the size of majority and minority, the longer the response latency (Study 1a). Furthermore, participants were aware of their own minority position (Study 1b). In Study 2, when participants were deprived of cognitive resources, MSE disappeared, presumably because participants lack the cognitive resources required to conform to utterance interpretation as favoured by the majority.

In the current age of globalization, living abroad is becoming an increasingly common and highly sought after experience. Sojourners’ ability to adjust to a new culture can be affected by their existing attachments, internalized as intrapsychic environment, as well as their biological sensitivity to environment. This sensitivity can be partly attributed to one’s genomic endowments. As such, this prospective study sought to examine the differential effects of early experiences with parents and affection for home culture on young adults’ ability to adapt to a foreign culture ( n = 305, students who studied overseas for a semester) – specifically, the difficulties they experience – moderated by genetic susceptibility. An additional 258 students who did not travel overseas were included as a comparison group to demonstrate the uniqueness of intercultural adaptation. Current findings suggest that the maternal, paternal and cultural bondings or affections affect different aspects of intercultural adjustment. Maternal bonding affected sojourners’ relationships with host nationals, while paternal bonding affected sojourners’ adjustment to a new physical environment. Moreover, individuals’ genetic predispositions significantly moderate these main effects regarding how much difficulty the sojourners experienced overseas.

Laminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA.

AIMS We identified an autosomal dominant non-sense mutation (R225X) in exon 4 of the lamin A/C (LMNA) gene in a Chinese family spanning 3 generations with familial dilated cardiomyopathy (DCM). In present study, we aim to generate induced pluripotent stem cells derived cardiomyocytes (iPSC-CMs) from an affected patient with R225X and another patient bearing LMNA frame-shift mutation for drug screening. METHODS and RESULTS Higher prevalence of nuclear bleb formation and micronucleation was present in LMNAR225X/WT and LMNAFramshift/WT iPSC-CMs. Under field electrical stimulation, percentage of LMNA-mutated iPSC-CMs exhibiting nuclear senescence and cellular apoptosis markedly increased. shRNA knockdown of LMNA replicated those phenotypes of the mutated LMNA field electrical stress. Pharmacological blockade of ERK1/2 pathway with MEK1/2 inhibitors, U0126 and selumetinib (AZD6244) significantly attenuated the pro-apoptotic effects of field electric stimulation on the mutated LMNA iPSC-CMs. CONCLUSION LMNA-related DCM was modeled in-vitro using patient-specific iPSC-CMs. Our results demonstrated that haploinsufficiency due to R225X LMNA non-sense mutation was associated with accelerated nuclear senescence and apoptosis of iPSC- CMs under electrical stimulation, which can be significantly attenuated by therapeutic blockade of stress-related ERK1/2 pathway.

People tend to make self-aggrandizing social comparisons on traits that are important to the self. However, existing research on the better-than-average effect (BTAE) and trait importance does not distinguish between personal trait importance (participants’ ratings of the importance of certain traits to themselves) and cultural trait importance (participants’ perceptions of the importance of the traits to the cultural group to which they belong). We demonstrated the utility of this distinction by examining the joint effects of personal importance and cultural importance on the BTAE among Hong Kong Chinese and American participants. Results showed that the BTAE was more pronounced for personally important traits among both Chinese and American participants. More important, the magnitude of the BTAE was smaller on culturally important traits among Chinese participants only. Chinese participants displayed the strongest BTAE on personally important and culturally unimportant traits, and the smallest BTAE on personally unimportant and culturally important ones. American participants showed the smallest BTAE on personally and culturally unimportant traits. These findings underscore the importance of distinguishing personal trait importance and cultural trait importance in understanding the cultural effects on self-aggrandizing social comparisons. They further suggest that in cultures where people are expected to be modest in self-expression (e.g., Chinese culture), people would avoid claiming superiority on highly culturally important traits even when these traits are important to the self.

This article reports three experiments that examined the association between (a) appearances and perceived capabilities of robots, (b) appearance and capabilities of robots and liking for the robots, and (c) perceived capabilities of robots and judgments concerning their suitability for different occupations. In Experiment 1, the authors found that participants perceived human- and animal-like robots to have relatively more warmth-related (e.g., emotion) capabilities than machinelike robots have. In Experiment 2, the authors found that liking for robots was not affected by their human likeness or their having warmth or competence capabilities. In Experiment 3, participants generally thought that robots should have information-processing and communication capabilities more than sensory and emotion capabilities. More interestingly, participants considered robots with different capabilities to be suitable for different occupations, preferring robots with emotion capabilities more in occupations that require frequent interactions with humans than in occupations that do not.

Synergistic Effects of I K1 and I f Currents. Introduction: Normal heart rhythms originate in the sinoatrial node. HCN-encoded funny current (I f) and the Kir2-encoded inward rectifier (I K1) counteract each other by respectively oscillating and stabilizing the negative resting membrane potential, and controlling action potential firing. Therefore, I K1 suppression and I f overexpression have been independently exploited to convert cardiomyocytes (CMs) into AP-firing bioartificial pacemakers. Although the 2 strategies have been largely assumed synergistic, their complementarity has not been investigated. Methods and Results: We explored the interrelationships of automaticity, I f and I K1 by transducing single left ventricular (LV) CMs isolated from guinea pig hearts with the recombinant adenoviruses Ad-CMV-GFP-IRES-HCN1- ÄÄÄ and/or Ad-CGI-Kir2.1 to mediate their current densities via a whole-cell patch clamp technique at 37°C. Results showed that Ad-CGI-HCN1-ÄÄÄ but not Ad-CGI-Kir2.1 transduction induced automaticity (181.1 ± 13.1 bpm). Interestingly, Ad-CGI-HCN1- ÄÄÄ/Ad-CGI-Kir2.1 cotransduction significantly promoted the induced firing frequency (320.0 ± 15.8 bpm; P < 0.05). Correlation analysis revealed that the firing frequency, phase-4 slope and APD 90 of AP-firing LV CMs were correlated with I f (R 2 > 0.7) only when -2 >I K1 >-4 pA/pF but not with I K1 over the entire I f ranges examined (0.02 < R 2 < 0.4). Unlike I f, I K1 displayed correlation with neither the phase-4 slope (R 2 = 0.02) nor phase-4 length (R 2 = 0.04) when -2 > I f > -4 pA/pF. As anticipated, however, APD 90 was correlated with I K1 (R 2 = 0.4). Conclusion: We conclude that an optimal level of I K1 maintains a voltage range for I f to operate most effectively during a dynamic cardiac cycle. (J Cardiovasc Electrophysiol, Vol. 20, pp. 1048-1054) © 2009 Wiley Periodicals, Inc., link_to_OA_fulltext

The current study tests an implication of the Associative-Propositional Evaluation model of implicit and explicit attitude measures in Hong Kong's intergroup context. We argued that the Implicit Association Test taps associative intergroup evaluations that are not necessarily consistent with the propositional implications of one's social identification inclusiveness and need for closure. In contrast, explicit intergroup attitude measures tap propositional evaluations resulting from validating the inferences drawn from pertinent propositional information in the evaluation context. Thus, explicit intergroup attitude should be consistent with the propositional implications of social identification inclusiveness and need for closure. We tested and found support for these hypotheses in a study of Hong Kong adolescents' (N = 65) perception of Hong Kong people and Mainland Chinese.

Management of terror of death and its subsequent reactions has been held to be universal. However, with only a few exceptions empirical efforts have so far been focused on people from North American and European countries. Would Eastern philosophical traditions render differential management of the terror of death? The present research aimed at testing the generality of terror management in Hong Kong Chinese samples. Across four studies, we found robust and consistent mortality salience effects, which attest to the generality of terror management. As in previous studies, compared to control participants, mortality salient participants displayed a stronger ingroup bias in person evaluation (Studies 1, 3). Additionally, we found a robust mortality salience effect on intergroup bias in resource allocation (Studies 2A, 2B, 3), which has not been examined in previous terror management research.

Cross-cultural psychologists assume that core cultural values define to a large extent what a culture is. Typically, core values are identified through an actual self-importance approach, in which core values are those that members of the culture as a group strongly endorse. In this article, the authors propose a perceived cultural importance approach to identifying core values, in which core values are values that members of the culture as a group generally believe to be important in the culture. In 5 studies, the authors examine the utility of the perceived cultural importance approach. Results consistently showed that, compared with values of high actual self-importance, values of high perceived cultural importance play a more important role in cultural identification. These findings have important implications for conceptualizing and measuring cultures.

In this study, we compared the endothelium-dependent and -independent relaxation of the isolated thoracic aorta of control (+db/+m) and diabetic (+db/+db) (C57BL/KsJ) mice. The gene expression (mRNA and protein) level of the muscarinic M(3) receptors, endothelial nitric oxide synthase (eNOS) and caveolin-1 of the aorta was also evaluated. Acetylcholine caused a concentration-dependent, N(G)-nitro-L-arginine methyl-ester (20 microM)-sensitive relaxation, with approximately 100% relaxation at 10 microM, in +db/+m mice. In +db/+db mice, the acetylcholine-induced relaxation was significantly smaller (maximum relaxation: approximately 80%). The sodium nitroprusside-mediated relaxation was slightly diminished in +db/+db mice, compared to +db/+m mice. However, there was no significant difference in the isoprenaline- and cromakalim-induced relaxation observed in both species. The mRNA and protein expression levels of caveolin-1 were significantly higher in the aorta of +db/+db mice. In contrast, there was no difference in the mRNA and protein expression levels of eNOS and muscarinic M(3) receptors between these mice. Our results demonstrate that the impairment of the acetylcholine-induced, endothelium-dependent aortic relaxation observed in +db/+db mice was probably associated with an enhanced expression of caveolin-1 mRNA and protein.

Previous research has shown a widespread bias among Hong Kong adolescents against Chinese Mainlanders. Based on social identity and social cognitive theories, we examined the effects of identity frame switching (situational induction of social category inclusiveness) and time pressure (environmental constraints on social information processing) on Hong Kong adolescents’ attitudes toward Chinese Mainlanders. Results indicated that Hong Kong adolescents had acquired a habitual tendency to make social comparisons within an exclusive regional framework of reference. This habitual tendency might lead to negative judgment biases toward Chinese Mainlanders, particularly when the adolescents made social judgments under time pressure. In addition, switching to an inclusive national frame of reference for social comparison attenuated negative intergroup attitudes. The theoretical implications of these findings are discussed.

Past research, with its emphasis on affective regulatory processes, has failed to find cross-cultural differences in counterfactual thoughts. In the current study, the authors examine the tendency to generate additive counterfactuals (those that focus on the addition of new aspects that were not in fact present) and subtractive counterfactuals (those that focus on subtraction of factual aspects) among Mainland Chinese and European American university students in five life domains: schoolwork, romantic relationships, family relationships, friendships, and life in general. As in previous studies, the authors find an overall main effect, in which additive counterfactuals predominate over subtractive counterfactuals within both cultural groups. However, they also find systematic cultural differences in the likelihood of generating additive and subtractive counterfactuals in the domains of schoolwork and family. These findings are discussed in terms of their implications for understanding the nature of cultural differences.

In two studies conducted in Hong Kong during and immediately after the outbreak of severe acute respiratory syndrome (SARS), participants displayed several social cognitive biases when they estimated the prevalence of and inferred the motives underlying SARS preventive behaviors. First, participants who practiced preventive behaviors (practicers) consistently estimated that more people practiced such behaviors than did non-practicers (false consensus bias). Second, for some preventive behaviors, participants believed that their own behaviors were more motivated by prosocial concerns (relative to self-interest) than were other practicers (pluralistic ignorance). Finally, non-practicers underestimated the importance of prosocial concerns underlying some preventive behaviors (actor-observer bias). We discussed the relevance of these social cognitive biases to health education and to Hong Kong people's psychological reactions to SARS.

Current models of interpersonal communication assume that estimation of listener's knowledge is a basis for message formulation. By introducing methodological modifications to the Fussell and Krauss (1992) paradigm, the present study provided more definitive evidence for the use of knowledge estimation in message productions. In the first experiment, participants indicated whether they knew each of 30 landmarks (thus providing the actual distribution of knowledge) and estimated the proportion of students who would know them. Participants' estimation of the relative distribution of knowledge corresponded impressively with the actual distribution. In the second experiment, a different group of participants described each of the landmarks to an intended audience. The length of the descriptions and the frequency of naming a landmark were predicted by the estimated identifiability from Experiment 1. These results replicated previous findings in a different culture and addressed unresolved issues relat...

In view of the recent development of macro-level theories concerning the spatial and temporal distribution of social representations, this paper presents a conceptualization of the evolution of shared beliefs from individual interactions, focusing on the role of communication. Drawing on the existing research literature and our own research findings on communication and cognition, we argue that the reciprocal relationship between shared reality and communication enables the development of systems of social representations at an individual level. Specifically, when formulating and comprehending messages, communicative partners draw on what they estimate to be shared knowledge among them. In addition, while communicating, communicative partners also strive to form shared representations of the topic of communication, which may overshadow pre-existing nonlinguistic representations. Moreover, contextual factors that influence communication also affect the development of shared reality. Based on these...

Elfin (previously named CLIM1) is a protein that possesses an N-terminal PDZ domain and a C-terminal LIM domain. It belongs to the family of Enigma proteins. Enigma proteins are a family of cytoplasmic proteins that contain an N-terminal PDZ domain and a series of C-terminal LIM domains. By virtue of these two protein interacting domains, Enigma proteins are capable of protein–protein interactions. It has been proposed that Enigma proteins may act as adapters between kinases and the cytoskeleton. We have previously shown that Elfin is most abundantly expressed in the heart and it colocalizes with α-actinin 2 at the Z-disks of the myocardium. In this report, Elfin was shown to localize at the actin stress fibers of myoblasts, as revealed by green fluorescent protein (GFP) tagging. In situ hybridization and immunostaining showed that Elfin expression begins at an early stage in mouse development and is present throughout the developing heart. Taken together, our experimental results suggest that Elfin may play an important role in myofibrillogenesis and heart development. J. Cell. Biochem. 83: 463–472, 2001. © 2001 Wiley-Liss, Inc.

Enigma proteins are proteins that possess a PDZ domain at the amino terminal and one to three LIM domains at the carboxyl terminal. They are cytoplasmic proteins that are involved with the cytoskeleton and signal transduction pathway. By virtue of the two protein interacting domains, they are capable of protein-protein interactions. Here we report a study on a human Enigma protein hCLIM1, in particular. Our study describes the interaction of the human 36kDa carboxyl terminal LIM domain protein (hCLIM1), the human homologue of CLP36 in rat, with α-actinin 2, the skeletal muscle isoform of α-actinin. hCLIM1 protein was shown to interact with α-actinin 2 by yeast two-hybrid screening and immunochemical analyses. Yeast two-hybrid analyses also demonstrated that the LIM domain of hCLIM1 binds to the EF-hand region of α-actinin 2, defining a new mode of LIM domain interactions. Immunofluorescent study demonstrates that hCLIM1 colocalizes with α-actinin at the Z-disks in human myocardium. Taken together, our experimental results suggest that hCLIM1is a novel cytoskeletal protein and may act as an adapter that brings other proteins to the cytoskeleton. J. Cell. Biochem. 78:558–565, 2000. © 2000 Wiley-Liss, Inc.

This study investigated if modernity and Confucian values were ingroups positively valued distinctiveness for Hong Kong adolescents with different social identities. Participants (236 Hong Kong adolescents) filled out a questionnaire which tapped social identity and intergroup perception. They also participated in a card-sorting activity in which they decided if any of 20 attributes (e.g., advanced, respecting collective will) could be used to characterize a specific ethnic–social group (e.g., mainland Chinese, Hongkongers, Americans). Multidimensional scaling performed on the card-sorting data resulted in a two-dimensional solution. Emphasis on Dimension 1 (modernity) correlated with positive perception of Hong Kong and Hong Kong people while emphasis on Dimension 2 (Confucian values) correlated with positive perception of China and Chinese. In addition, compared to adolescents who identified themselves as Chinese or Chinese-Hongkongers, those who identified themselves as Hongkongers or Hongkonger-Chinese placed more emphasis on modernity and less on Confucian values. The results were discussed with reference to Taj fels theory of social identity.

The thalassemias are common in Hong Kong. One of the severe forms, beta-thalassemia major, has been preventable locally by antenatal screening since 1983. Yet new patients are still being diagnosed. In this retrospective study, 34 children with severe beta-thalassemia syndromes were diagnosed in two major public hospitals between 1990 and 1996. They included one pair of identical twins and two pairs of siblings. Twenty-seven (79%) had homozygous beta-thalassemia and seven (21%) had beta E thalassemia. All but four (12%) were transfusion dependent. Fifty-five (89%) parents had been evaluated for their thalassemia status. Forty-eight had beta-thalassemia traits and seven were hemoglobin E carriers. The reasons for the birth of these children with severe beta-thalassemia syndromes were (1) late or no antenatal visit (n = 8, 24.2%), including three cross-border deliveries in which the pregnant mothers came from mainland China to Hong Kong for confinement, (2) lack of maternal screening (n = 13, 39.4%), (3) lack of paternal screening (n = 7, 21.2%), (4) parental refusal (n = 3, 9.1%), and (5) unknown (n = 2, 6.1%). These findings suggest that several factors undermine the effectiveness of antenatal screening for prevention of thalassemias. Many medical practitioners and the general public are still not aware of the screening procedures. The migration of population from mainland China to Hong Kong may result in the birth of many more children with beta-thalassemia major.

Friedreich ataxia (FRDA), a recessive neurodegenerative disorder commonly associated with hypertrophic cardiomyopathy, is due to GAA repeat expansions within the first intron of the frataxin (FXN) gene encoding the mitochondrial protein involved in iron-sulfur cluster biosynthesis. The triplet codon repeats lead to heterochromatin-mediated gene silencing and loss of frataxin. Nevertheless, inadequacy of existing FRDA-cardiac cellular models limited cardiomyopathy studies. We tested the hypothesis that iron homeostasis deregulation accelerates reduction in energy synthesis dynamics which contributes to impaired cardiac calcium homeostasis and contractile force. Silencing of FXN expressions occurred both in somatic FRDA-skin fibroblasts and two of the induced pluripotent stem cells (iPSC) clones; a sign of stress condition was shown in FRDA-iPSC cardiomyocytes with disorganized mitochondrial network and mitochondrial DNA (mtDNA) depletion; hypertrophic cardiac stress responses were observed by an increase in α-actinin-positive cell sizes revealed by FACS analysis as well as elevation in brain natriuretic peptide (BNP) gene expression; the intracellular iron accumulated in FRDA cardiomyocytes might be due to attenuated negative feedback response of transferring receptor (TSFR) expression and positive feedback response of ferritin (FTH1); energy synthesis dynamics, in terms of ATP production rate, was impaired in FRDA-iPSC cardiomyocytes, which were prone to iron overload condition. Energetic insufficiency determined slower Ca(2+) transients by retarding calcium reuptake to sarcoplasmic reticulum (SR) and impaired the positive inotropic and chronotropic responses to adrenergic stimulation. Our data showed for the first time that FRDA-iPSCs cardiac derivatives represent promising models to study cardiac stress response due to impaired iron homeostasis condition and mitochondrial damages. The cardiomyopathy phenotype was accelerated in an iron-overloaded condition early in calcium homeostasis aspect.