60 research outputs found

    The Metaphor of Circle: Stanislavski, Phenomenology of Roundness and High Yoga

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    Stanislavski’s Eastern influence and his persistent fascination with Yoga is an established area of research. Stanislavski has two major yogic influences in the System: Hatha Yoga and Raja Yoga. The first is about training the body through postures, movements, stances and breathing exercises to make it active, relaxed and energetic. The second includes a range of exclusive practices on concentration and visualization that are an integral part of the actor’s creativity. However, in the current research, there is a clear lack of a comprehensive practical method that informs Stanislavski’s use of yogic practice in the System: what specific yogic exercises were used and what synergies were developed in the training? Scholars have, so far, only explored Stanislavski’s literary legacy of his encounter with yoga, identifying the Sanskrit terms appeared in his writings such as prana for breathing and the Indian anecdotes he used when answering the questions of his students. Focusing on the metaphor of the circle, the phenomenology of roundness and the Deleuzian notions of ‘the invisible forces of sensations’ and ‘the body becomes an event itself’, the present study, for the first time, offers useful insights into the fundamental principles of yoga and their methods of practice as a way of developing a new training to understand the significance of Stanislavski in the 21st century

    Ultra-Sharp Nanowire Arrays Natively Permeate, Record, and Stimulate Intracellular Activity in Neuronal and Cardiac Networks

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    Intracellular access with high spatiotemporal resolution can enhance our understanding of how neurons or cardiomyocytes regulate and orchestrate network activity, and how this activity can be affected with pharmacology or other interventional modalities. Nanoscale devices often employ electroporation to transiently permeate the cell membrane and record intracellular potentials, which tend to decrease rapidly to extracellular potential amplitudes with time. Here, we report innovative scalable, vertical, ultra-sharp nanowire arrays that are individually addressable to enable long-term, native recordings of intracellular potentials. We report large action potential amplitudes that are indicative of intracellular access from 3D tissue-like networks of neurons and cardiomyocytes across recording days and that do not decrease to extracellular amplitudes for the duration of the recording of several minutes. Our findings are validated with cross-sectional microscopy, pharmacology, and electrical interventions. Our experiments and simulations demonstrate that individual electrical addressability of nanowires is necessary for high-fidelity intracellular electrophysiological recordings. This study advances our understanding of and control over high-quality multi-channel intracellular recordings, and paves the way toward predictive, high-throughput, and low-cost electrophysiological drug screening platforms.Comment: Main manuscript: 33 pages, 4 figures, Supporting information: 43 pages, 27 figures, Submitted to Advanced Material

    RLIP76, a Glutathione-Conjugate Transporter, Plays a Major Role in the Pathogenesis of Metabolic Syndrome

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    PURPOSE: Characteristic hypoglycemia, hypotriglyceridemia, hypocholesterolemia, lower body mass, and fat as well as pronounced insulin-sensitivity of RLIP76⁻/⁻ mice suggested to us the possibility that elevation of RLIP76 in response to stress could itself elicit metabolic syndrome (MSy). Indeed, if it were required for MSy, drugs used to treat MSy should have no effect on RLIP76⁻/⁻ mice. RESEARCH DESIGN AND METHODS: Blood glucose (BG) and lipid measurements were performed in RLIP76⁺/⁺ and RLIP76⁻/⁻ mice, using Ascensia Elite Glucometer® for glucose and ID Labs kits for cholesterol and triglycerides assays. The ultimate effectors of gluconeogenesis are the three enzymes: PEPCK, F-1,6-BPase, and G6Pase, and their expression is regulated by PPARγ and AMPK. The activity of these enzymes was tested by protocols standardized by us. Expressions of RLIP76, PPARα, PPARγ, HMGCR, pJNK, pAkt, and AMPK were performed by Western-blot and tissue staining. RESULTS: The concomitant activation of AMPK and PPARγ by inhibiting transport activity of RLIP76, despite inhibited activity of key glucocorticoid-regulated hepatic gluconeogenic enzymes like PEPCK, G6Pase and F-1,6-BP in RLIP76⁻/⁻ mice, is a salient finding of our studies. The decrease in RLIP76 protein expression by rosiglitazone and metformin is associated with an up-regulation of PPARγ and AMPK. CONCLUSIONS/SIGNIFICANCE: All four drugs, rosiglitazone, metformin, gemfibrozil and atorvastatin failed to affect glucose and lipid metabolism in RLIP76⁻/⁻ mice. Studies confirmed a model in which RLIP76 plays a central role in the pathogenesis of MSy and RLIP76 loss causes profound and global alterations of MSy signaling functions. RLIP76 is a novel target for single-molecule therapeutics for metabolic syndrome

    Younger age of escalation of cardiovascular risk factors in Asian Indian subjects

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    <p>Abstract</p> <p>Background</p> <p>Cardiovascular risk factors start early, track through the young age and manifest in middle age in most societies. We conducted epidemiological studies to determine prevalence and age-specific trends in cardiovascular risk factors among adolescent and young urban Asian Indians.</p> <p>Methods</p> <p>Population based epidemiological studies to identify cardiovascular risk factors were performed in North India in 1999–2002. We evaluated major risk factors-smoking or tobacco use, obesity, truncal obesity, hypertension, dysglycemia and dyslipidemia using pre-specified definitions in 2051 subjects (male 1009, female 1042) aged 15–39 years of age. Age-stratified analyses were performed and significance of trends determined using regression analyses for numerical variables and Χ<sup>2 </sup>test for trend for categorical variables. Logistic regression was used to identify univariate and multivariate odds ratios (OR) for correlation of age and risk factors.</p> <p>Results</p> <p>In males and females respectively, smoking or tobacco use was observed in 200 (11.8%) and 18 (1.4%), overweight or obesity (body mass index, BMI ≥ 25 kg/m<sup>2</sup>) in 12.4% and 14.3%, high waist-hip ratio, WHR (males > 0.9, females > 0.8) in 15% and 32.3%, hypertension in 5.6% and 3.1%, high LDL cholesterol (≥ 130 mg/dl) in 9.4% and 8.9%, low HDL cholesterol (<40 mg/dl males, <50 mg/dl females) in 16.2% and 49.7%, hypertriglyceridemia (≥ 150 mg/dl) in 9.7% and 6%, diabetes in 1.0% and 0.4% and the metabolic syndrome in 3.4% and 3.6%. Significantly increasing trends with age for indices of obesity (BMI, waist, WHR), glycemia (fasting glucose, metabolic syndrome) and lipids (cholesterol, LDL cholesterol, HDL cholesterol) were observed (p for trend < 0.01). At age 15–19 years the prevalence (%) of risk factors in males and females, respectively, was overweight/obesity in 7.6, 8.8; high WHR 4.9, 14.4; hypertension 2.3, 0.3; high LDL cholesterol 2.4, 3.2; high triglycerides 3.0, 3.2; low HDL cholesterol 8.0, 45.3; high total:HDL ratio 3.7, 4.7, diabetes 0.0 and metabolic syndrome in 0.0, 0.2 percent. At age groups 20–29 years in males and females, ORs were, for smoking 5.3, 1.0; obesity 1.6, 0.8; truncal obesity 4.5, 3.1; hypertension 2.6, 4.8; high LDL cholesterol 6.4, 1.8; high triglycerides 3.7, 0.9; low HDL cholesterol 2.4, 0.8; high total:HDL cholesterol 1.6, 1.0; diabetes 4.0, 1.0; and metabolic syndrome 37.7, 5.7 (p < 0.05 for some). At age 30–39, ORs were- smoking 16.0, 6.3; overweight 7.1, 11.3; truncal obesity 21.1, 17.2; hypertension 13.0, 64.0; high LDL cholesterol 27.4, 19.5; high triglycerides 24.2, 10.0; low HDL cholesterol 15.8, 14.1; high total:HDL cholesterol 37.9, 6.10; diabetes 50.7, 17.4; and metabolic syndrome 168.5, 146.2 (p < 0.01 for all parameters). Multivariate adjustment for BMI, waist size and WHR in men and women aged 30–39 years resulted in attenuation of ORs for hypertension and dyslipidemias.</p> <p>Conclusion</p> <p>Low prevalence of multiple cardiovascular risk factors (smoking, hypertension, dyslipidemias, diabetes and metabolic syndrome) in adolescents and rapid escalation of these risk factors by age of 30–39 years is noted in urban Asian Indians. Interventions should focus on these individuals.</p

    Effects of xenobiotics and peroxisome proliferator-activated receptor-alpha on the human UDPglucose dehydrogenase gene expression

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    [[abstract]]During drug metabolism, UDPglucuronate, a product of the reaction catalyzed by the enzyme UDPglucose dehydrogenase (UGDH), is conjugated with the metabolites to facilitate their elimination. So far, it is not known whether xenobiotics can modulate the UGDH gene expression. This question was tested by treating the human hepatoma cells HepG2 with several medicinal compounds and the UGDH gene expression analyzed by using real-time PCR. Both eugenol and rifampicin showed activation of the gene expression. Piperine showed slight downregulation of the UGDH gene expression, whereas no effect was observed with acetaminophen treatment. Through promoter-reporter gene assays, we found that rifampicin showed multiple-folds activation of a 1.23-kb UGDH promoter construct, and the region likely to respond to rifampicin treatment is located within the range -632 to -1050. A bioinformatics search for xenobiotic response element in this region has predicted a binding motif for the peroxisome proliferator-activated receptor-alpha(PPAR alpha) at position -1003. A mutation at the predicted PPAR recognizing motif eliminated normal suppression as well as the rifampicin activation effect on the UGDH promoter activity. Cotransfection with the PPAR alpha and retinoid X receptor-alpha expression vectors and subsequent treatment with the PPAR alpha agonist led to the suppression of the UGDH promoter activity either in the presence or absence of rifampicin. Our study, for the first time, shows the UGDH gene to be under xenobiotic regulation and delineates a motif responsible for rifampicin response and transcriptional repression of the UGDH gene

    Sumoylation of eIF4E activates mRNA translation

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    Considerations and recent advances in nanoscale interfaces with neuronal and cardiac networks

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    Nanoscale interfaces with biological tissue, principally made with nanowires (NWs), are envisioned as minimally destructive to the tissue and as scalable tools to directly transduce the electrochemical activity of a neuron at its finest resolution. This review lays the foundations for understanding the material and device considerations required to interrogate neuronal activity at the nanoscale. We first discuss the electrochemical nanoelectrode-neuron interfaces and then present new results concerning the electrochemical impedance and charge injection capacities of millimeter, micrometer, and nanometer scale wires with Pt, PEDOT:PSS, Si, Ti, ITO, IrOx, Ag, and AgCl materials. Using established circuit models for NW-neuron interfaces, we discuss the impact of having multiple NWs interfacing with a single neuron on the amplitude and temporal characteristics of the recorded potentials. We review state of the art advances in nanoelectrode-neuron interfaces, the standard control experiments to investigate their electrophysiological behavior, and present recent high fidelity recordings of intracellular potentials obtained with ultrasharp NWs developed in our laboratory that naturally permeate neuronal cell bodies. Recordings from arrays and individually addressable electrically shorted NWs are presented, and the long-term stability of intracellular recording is discussed and put in the context of established techniques. Finally, a perspective on future research directions and applications is presented

    Knowledge of human immunodeficiency virus, attitudes, and willingness to conduct human immunodeficiency virus testing among Indian dentists

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    Context: India has the third-highest number of people living with human immunodeficiency virus (HIV) in the world. Early diagnosis can prevent HIV transmission and since a large proportion of the Indian population are likely to be seen in a dental setting, it may serve as an important site for early HIV diagnosis. Aims: The aim of this study was to investigate the knowledge of HIV, attitudes, and willingness to conduct HIV testing among Indian dentists. Settings: A cross-sectional survey of 503 Indian dentists was conducted in Delhi, Gandhinagar, Bhubaneswar, and Hyderabad (representing low, moderate, and high HIV prevalence areas). Subjects and Methods: HIV knowledge was measured using the HIV-KQ-18, and attitudes and willingness were examined. Statistical Analysis Used: Descriptive analysis and Chi-square test were performed using SPSS version 21. Results: A third of the respondents had a high HIV knowledge score. High knowledge scores were positively associated with age group, level of education, and dental specialty. Over 73% were willing to deliver HIV-positive test results. Almost 80% of the respondents felt that rapid HIV testing was needed in a dental setting. Attitudes and willingness were found to be significantly related to the survey site suggesting cultural difference as an important factor in taking up HIV testing. Conclusions: General awareness of HIV among this sample of Indian dentists appears to be low. The findings from this study however suggest that Indian dentists have expressed a need for rapid HIV testing in dental setting with a strong emphasis on the need for further education on HIV testing
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