Differences in the Pathways of Proteins Unfolding Induced by Urea and Guanidine Hydrochloride: Molten Globule State and Aggregates

It was shown that at low concentrations guanidine hydrochloride (GdnHCl) can cause aggregation of proteins in partially folded state and that fluorescent dye 1-anilinonaphthalene-8-sulfonic acid (ANS) binds with these aggregates rather than with hydrophobic clusters on the surface of protein in molten globule state. That is why the increase in ANS fluorescence intensity is often recorded in the pathway of protein denaturation by GdnHCl, but not by urea. So what was previously believed to be the molten globule state in the pathway of protein denaturation by GdnHCl, in reality, for some proteins represents the aggregates of partially folded molecules

Use of television, videogames, and computer among children and adolescents in Italy

<p>Abstract</p> <p>Background</p> <p>This survey determined the practices about television (video inclusive), videogames, and computer use in children and adolescents in Italy.</p> <p>Methods</p> <p>A self-administered anonymous questionnaire covered socio-demographics; behaviour about television, videogames, computer, and sports; parental control over television, videogames, and computer.</p> <p>Results</p> <p>Overall, 54.1% and 61% always ate lunch or dinner in front of the television, 89.5% had a television in the bedroom while 52.5% of them always watched television there, and 49% indicated that parents controlled the content of what was watched on television. The overall mean length of time daily spent on television viewing (2.8 hours) and the frequency of watching for at least two hours per day (74.9%) were significantly associated with older age, always ate lunch or dinner while watching television, spent more time playing videogames and using computer. Those with parents from a lower socio-economic level were also more likely to spend more minutes viewing television. Two-thirds played videogames for 1.6 daily hours and more time was spent by those younger, males, with parents that do not control them, who watched more television, and who spent more time at the computer. The computer was used by 85% of the sample for 1.6 daily hours and those older, with a computer in the bedroom, with a higher number of computers in home, who view more television and play videogames were more likely to use the computer.</p> <p>Conclusion</p> <p>Immediate and comprehensive actions are needed in order to diminish time spent at the television, videogames, and computer.</p

Risk Factors for Obesity and High Blood Pressure in Chinese American Children: Maternal Acculturation and Children’s Food Choices

The objective of this study is to explore risk factors associated with overweight and high blood pressure in Chinese American children. Students and their parents were recruited from Chinese language schools in the San Francisco Bay Area. Data were collected on 67 children and their mothers, and included children’s weight, height, waist and hip circumferences, blood pressure, level of physical activity, dietary intake, usual food choice, knowledge about nutrition and physical activity, and self-efficacy regarding diet and physical activity. Mothers completed questionnaires on demographic data and acculturation. About 46% of children had a body mass index exceeding the 85th percentile. Lower level of maternal acculturation is a risk factor for overweight and higher waist to hip ratio. Children’s unhealthy food choices were predictive of high body mass index and high systolic blood pressure, whereas older age and less physical activity in children were predictors of high diastolic blood pressure. Developing culturally sensitive and developmentally appropriate interventions to reduce overweight and high blood pressure is critical to reduce health disparities among minority children

Tension and Robustness in Multitasking Cellular Networks

Cellular networks multitask by exhibiting distinct, context-dependent dynamics. However, network states (parameters) that generate a particular dynamic are often sub-optimal for others, defining a source of “tension” between them. Though multitasking is pervasive, it is not clear where tension arises, what consequences it has, and how it is resolved. We developed a generic computational framework to examine the source and consequences of tension between pairs of dynamics exhibited by the well-studied RB-E2F switch regulating cell cycle entry. We found that tension arose from task-dependent shifts in parameters associated with network modules. Although parameter sets common to distinct dynamics did exist, tension reduced both their accessibility and resilience to perturbation, indicating a trade-off between “one-size-fits-all” solutions and robustness. With high tension, robustness can be preserved by dynamic shifting of modules, enabling the network to toggle between tasks, and by increasing network complexity, in this case by gene duplication. We propose that tension is a general constraint on the architecture and operation of multitasking biological networks. To this end, our work provides a framework to quantify the extent of tension between any network dynamics and how it affects network robustness. Such analysis would suggest new ways to interfere with network elements to elucidate the design principles of cellular networks

A Systematic Analysis of Cell Cycle Regulators in Yeast Reveals That Most Factors Act Independently of Cell Size to Control Initiation of Division

Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene deletions that altered cell cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell cycle control mechanisms. We found that CBS, which catalyzes the synthesis of cystathionine from serine and homocysteine, advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function, which does not require CBS's catalytic activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Taken together, these findings significantly expand the range of factors required for the timely initiation of cell division. The systematic identification of non-essential regulators of cell division we describe will be a valuable resource for analysis of cell cycle progression in yeast and other organisms

Feasibility, design and conduct of a pragmatic randomized controlled trial to reduce overweight and obesity in children: The electronic games to aid motivation to exercise (eGAME) study

<p>Abstract</p> <p>Background</p> <p>Childhood obesity has reached epidemic proportions in developed countries. Sedentary screen-based activities such as video gaming are thought to displace active behaviors and are independently associated with obesity. Active video games, where players physically interact with images onscreen, may have utility as a novel intervention to increase physical activity and improve body composition in children. The aim of the Electronic Games to Aid Motivation to Exercise (eGAME) study is to determine the effects of an active video game intervention over 6 months on: body mass index (BMI), percent body fat, waist circumference, cardio-respiratory fitness, and physical activity levels in overweight children.</p> <p>Methods/Design</p> <p>Three hundred and thirty participants aged 10–14 years will be randomized to receive either an active video game upgrade package or to a control group (no intervention).</p> <p>Discussion</p> <p>An overview of the eGAME study is presented, providing an example of a large, pragmatic randomized controlled trial in a community setting. Reflection is offered on key issues encountered during the course of the study. In particular, investigation into the feasibility of the proposed intervention, as well as robust testing of proposed study procedures is a critical step prior to implementation of a large-scale trial.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry ACTRN12607000632493</p

Excessive TV viewing and cardiovascular disease risk factors in adolescents. The AVENA cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Excessive television (TV) viewing might play an important role in the development of cardiovascular disease (CVD). The aim of this study was to examine the independent associations between TV viewing and CVD risk factors in adolescents.</p> <p>Methods</p> <p>A sample of 425 adolescents, aged 13- to 18.5-year-old, was included in this study. Body mass index (BMI), waist circumference (WC), glucose, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein (apo) A-1, apo B-100, and lipoprotein(a) levels were determined. A composite CVD risk score was computed based on age-, sex-, sexual maturation- and race-standardized triglycerides, HDL-cholesterol, LDL-cholesterol and glucose. TV viewing was self-reported.</p> <p>Results</p> <p>Two hundred and twenty-five adolescents (53%) who spent >3 hrs/day watching TV were considered as the "high TV viewing" group. Ninety-nine adolescents (23%) from the total sample were classified as overweight according to International age- and sex-specific BMI values. The high TV viewing group had significantly less favorable values of HDL-cholesterol, glucose, apo A1 and CVD score, independent of age, sex, sexual maturation, race and weight status. There was a significant interaction effect of TV viewing × weight status (P = 0.002) on WC, and the negative influence of TV viewing on WC persisted in the overweight group (P = 0.031) but was attenuated in non-overweight adolescents (P > 0.05).</p> <p>Conclusion</p> <p>Excessive TV viewing seems to be related to an unfavorable CVD risk factors profile in adolescence. Reducing TV viewing in overweight adolescents might be beneficial to decrease abdominal body fat.</p

Evidence for the Complexity of MicroRNA-Mediated Regulation in Ovarian Cancer: A Systems Approach

MicroRNAs (miRNAs) are short (∼22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. Previous studies have shown that miRNAs inhibit the translation and facilitate the degradation of their targeted messenger RNAs (mRNAs) making them attractive candidates for use in cancer therapy. However, the potential clinical utility of miRNAs in cancer therapy rests heavily upon our ability to understand and accurately predict the consequences of fluctuations in levels of miRNAs within the context of complex tumor cells. To evaluate the predictive power of current models, levels of miRNAs and their targeted mRNAs were measured in laser captured micro-dissected (LCM) ovarian cancer epithelial cells (CEPI) and compared with levels present in ovarian surface epithelial cells (OSE). We found that the predicted inverse correlation between changes in levels of miRNAs and levels of their mRNA targets held for only ∼11% of predicted target mRNAs. We demonstrate that this low inverse correlation between changes in levels of miRNAs and their target mRNAs in vivo is not merely an artifact of inaccurate miRNA target predictions but the likely consequence of indirect cellular processes that modulate the regulatory effects of miRNAs in vivo. Our findings underscore the complexities of miRNA-mediated regulation in vivo and the necessity of understanding the basis of these complexities in cancer cells before the therapeutic potential of miRNAs can be fully realized

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.Journal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov'tSCOPUS: re.jinfo:eu-repo/semantics/publishe

Self-reported screen time and cardiometabolic risk in obese dutch adolescents

BACKGROUND: It is not clear whether the association between sedentary time and cardiometabolic risk exists among obese adolescents. We examined the association between screen time (TV and computer time) and cardiometabolic risk in obese Dutch adolescents. METHODS AND FINDINGS: For the current cross-sectional study, baseline data of 125 Dutch overweight and obese adolescents (12-18 years) participating in the Go4it study were included. Self-reported screen time (Activity Questionnaire for Adolescents and Adults) and clustered and individual cardiometabolic risk (i.e. body composition, systolic and diastolic blood pressure, low-density (LDL-C), high-density (HDL-C) and total cholesterol (TC), triglycerides, glucose and insulin) were assessed in all participants. Multiple linear regression analyses were used to assess the association between screen time and cardiometabolic risk, adjusting for age, gender, pubertal stage, ethnicity and moderate-to-vigorous physical activity. We found no significant relationship between self-reported total screen time and clustered cardiometabolic risk or individual risk factors in overweight and obese adolescents. Unexpectedly, self-reported computer time, but not TV time, was slightly but significantly inversely associated with TC (B = -0.002; CI = [-0.003;-0.000]) and LDL-C (B = -0.002; CI = [-0.001;0.000]). CONCLUSIONS: In obese adolescents we could not confirm the hypothesised positive association between screen time and cardiometabolic risk. Future studies should consider computer use as a separate class of screen behaviour, thereby also discriminating between active video gaming and other computer activities