Phospholemman: a novel cardiac stress protein.

Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. Functionally, when phosphorylated at serine(68), PLM stimulates Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L-type Ca(2+) channel. Therefore, PLM occupies a key modulatory role in intracellular Na(+) and Ca(2+) homeostasis and is intimately involved in regulation of excitation-contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na(+) overload and simultaneously preserves inotropy by inhibiting Na(+)/Ca(2+) exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and potentially L-type Ca(2+) channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189-196

Validation and reliability of the Physical Activity Scale for the Elderly in Chinese population

Objectives: Physical Activity Scale for the Elderly (PASE) is a widely used questionnaire in epidemiological studies for assessing the physical activity level of elderly. This study aims to translate and validate PASE in Chinese population. Design: Cross-sectional study. Subjects: Chinese elderly aged 65 or above. Methods: The original English version of PASE was translated into Chinese (PASE-C) following standardized translation procedures. Ninety Chinese elderly aged 65 or above were recruited in the community. Test-retest reliability was determined by comparing the scores obtained from two separate administrations by the intraclass correlation coefficient. Validity was evaluated by Spearman’s rank correlation coefficients between PASE and Medical Outcome Survey 36-Item Short Form Health Survey (SF-36), grip strength, single-leg-stance, 5 times sit-to-stand and 10-m walk. Results: PASE-C demonstrated good test-retest reliability (intraclass correlation coefficient  =0.81). Fair to moderate association were found between PASE-C and most of the subscales of SF-36 (rs=0.285 to 0.578, p<0.01), grip strength (rs=0.405 to 0.426, p<0.001), single-leg-stance (rs =0.470 to 0.548, p<0.001), 5 times sit-to-stand (rs =–0.33, p=0.001) and 10-m walk (rs =–0.281, p=0.007). Conclusion: PASE-C is a reliable and valid instrument for assessing the physical activity level of elderly in Chinese population

The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease

The B-cell lymphoma 2–associated anthanogene (BAG3) protein is expressed most prominently in the heart, the skeletal muscle, and in many forms of cancer. In the heart, it serves as a co-chaperone with heat shock proteins in facilitating autophagy; binds to B-cell lymphoma 2, resulting in inhibition of apoptosis; attaches actin to the Z disk, providing structural support for the sarcomere; and links the α-adrenergic receptor with the L-type Ca2+ channel. When BAG3 is overexpressed in cancer cells, it facilitates prosurvival pathways that lead to insensitivity to chemotherapy, metastasis, cell migration, and invasiveness. In contrast, in the heart, mutations in BAG3 have been associated with a variety of phenotypes, including both hypertrophic/restrictive and dilated cardiomyopathy. In murine skeletal muscle and vasculature, a mutation in BAG3 leads to critical limb ischemia after femoral artery ligation. An understanding of the biology of BAG3 is relevant because it may provide a therapeutic target in patients with both cardiac and skeletal muscle disease

Stable Isotope and Dental Caries Data Reveal Abrupt Changes in Subsistence Economy in Ancient China in Response to Global Climate Change

Prior to the introduction of wheat and barley from Central Asia during the Neolithic period, northern Chinese agricultural groups subsisted heavily on millet. Despite being the focus of many decades of intensive interest and research, the exact route(s), date(s), and mechanisms of the spread and adoption of wheat and barley into the existing well-established millet-based diet in northern China are still debated. As the majority of the important introduced crops are C3plants, while the indigenous millet is C4, archaeologists can effectively identify the consumption of any introduced crops using stable carbon isotope analysis. Here we examine published stable isotope and dental caries data of human skeletal remains from 77 archaeological sites across northern and northwestern China. These sites date between 9000 to 1750 BP, encompassing the period from the beginning of agriculture to wheat’s emergence as a staple crop in northern China. The aim of this study is to evaluate the implications of the spread and adoption of these crops in ancient China. Detailed analysis of human bone collagen&nbsp;δ13C values reveals an almost concurrent shift from a C4-based to a mixed C3/ C4– based subsistence economy across all regions at around 4500–4000 BP. This coincided with a global climatic event, Holocene Event 3 at 4200 BP, suggesting that the sudden change in subsistence economy across northern and northwestern China was likely related to climate change. Moreover, the substantially increased prevalence of dental caries from pre–to post–4000 BP indicates an increase in the consumption of cariogenic cereals during the later period. The results from this study have significant implications for understanding how the adoption of a staple crop can be indicative of large-scale environmental and socio-political changes in a region

Immunofluorescence Assay for Serologic Diagnosis of SARS

We evaluated a virus-infected cell-based indirect immunofluorescence assay for detecting anti–severe acute respiratory syndrome-associated coronavirus (SARS-CoV) immunoglobulin (Ig) G antibody. All confirmed SARS cases demonstrated seroconversion or fourfold rise in IgG antibody titer; no control was positive. Sensitivity and specificity of this assay were both 100%. Immunofluorescence assay can ascertain the status of SARS-CoV infection

Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro

Although peroxisome proliferator-activated receptor gamma (PPARγ) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARγ in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPAR

MICU1 Motifs Define Mitochondrial Calcium Uniporter Binding and Activity

SummaryResting mitochondrial matrix Ca2+ is maintained through a mitochondrial calcium uptake 1 (MICU1)-established threshold inhibition of mitochondrial calcium uniporter (MCU) activity. It is not known how MICU1 interacts with MCU to establish this Ca2+ threshold for mitochondrial Ca2+ uptake and MCU activity. Here, we show that MICU1 localizes to the mitochondrial matrix side of the inner mitochondrial membrane and MICU1/MCU binding is determined by a MICU1 N-terminal polybasic domain and two interacting coiled-coil domains of MCU. Further investigation reveals that MICU1 forms homo-oligomers, and this oligomerization is independent of the polybasic region. However, the polybasic region confers MICU1 oligomeric binding to MCU and controls mitochondrial Ca2+ current (IMCU). Moreover, MICU1 EF hands regulate MCU channel activity, but do not determine MCU binding. Loss of MICU1 promotes MCU activation leading to oxidative burden and a halt to cell migration. These studies establish a molecular mechanism for MICU1 control of MCU-mediated mitochondrial Ca2+ accumulation, and dysregulation of this mechanism probably enhances vascular dysfunction

Prevalence, incidence, and progression of myopia of school children

PURPOSE. To determine the prevalence, incidence, and progression of myopia of Chinese children in Hong Kong. METHODS. A cross-sectional survey was initially conducted. A longitudinal follow-up study was then conducted 12 months later. RESULTS. A total of 7560 children of mean age 9.33 (95% confidence interval [CI] ϭ 9.11-9.45; range, 5-16) participated in the study. Mean spherical equivalent refraction (SER) was Ϫ0.33 D (SD ϭ 11.56; range, Ϫ13.13 to ϩ14.25 D). Myopia (SER Յ Ϫ0.50 D) was the most common refractive error and was found in 36.71% Ϯ 2.87% (SD) of children. Prevalence of myopia correlated positively with older age. Children aged 11 years were almost 15 times more likely to have myopia than were children younger than 7 years (Odds ratio [OR] ϭ 14.81; 95% CI ϭ 14.17-15.48). Incidence of myopia was 144.1 Ϯ 2.31 (SD) per 1000 primary school children per annum. Increasing age was correlated with increased incidence of myopia, with highest risk in children ages 11 years (OR ϭ 2.27; 95% CI ϭ 2.11-2.44). The average annual change in SER for children with myopia (SER Յ Ϫ0.50 D) was Ϫ0.63 D (SD ϭ 3.44) compared with Ϫ0.29 D (SD ϭ 2.96) for those who were not myopic at the beginning of the study (P Ͻ 0.001). CONCLUSIONS. The results show that the prevalence and progression of myopia in Hong Kong children was much higher than those previously reported in Western countries. The longterm socioeconomic impact of these findings warrants further studies. (Invest Ophthalmol Vis Sci

Poor health literacy associated with stronger perceived barriers to breast cancer screening and overestimated breast cancer risk

BackgroundLow health literacy (HL) is negatively associated with mammography screening uptake. However, evidence of the links between poor HL and low mammography screening participation is scarce.MethodsWe conducted a cross-sectional questionnaire survey among participants of a cancer screening program. We measured HL using a validated Chinese instrument. We assessed breast cancer screening-related beliefs using the Health Belief Model and the accuracy of risk perception. We used multivariable regression models to estimate the relationship between HL and the outcomes.ResultsA total of 821 females were included. 264 (32.2%) had excellent or sufficient, 353 (43.0%) had problematic, and 204 (24.8%) had inadequate health literacy (IHL). Women with IHL were more likely to agree that high price (β = -0.211, 95% CI -0.354 to -0.069), lack of time (β = -0.219, 95% CI -0.351 to -0.088), inconvenient service time (β = -0.291, 95% CI -0.421 to -0.160), long waiting time (β = -0.305, 95% CI -0.447 to -0.164), fear of positive results (β = -0.200, 95% CI -0.342 to -0.058), embarrassment (β = -0.225, 95% CI -0.364 to -0.086), fear of pain (β = -0.154, 95% CI -0.298 to -0.010), fear of radiation (β = -0.177, 95% CI -0.298 to -0.056), lack of knowledge on service location (β = -0.475, 95% CI -0.615 to -0.335), and lack of knowledge on mammography (β = -0.360, 95% CI -0.492 to -0.228) were barriers. They were also less likely to have an accurate breast cancer risk perception (aOR 0.572, 95% CI 0.341 to 0.956).ConclusionWomen with lower HL could have stronger perceived barriers to BC screening and an over-estimation of their breast cancer risk. Tackling emotional and knowledge barriers, financial and logistical assistance, and guidance on risk perception are needed to increase their breast cancer screening uptake