Evaluation of effects caused by differentially spliced Ets-1 transcripts in fibroblasts

The transcription factor Ets-1 is known to be involved in a broad variety of cellular functions such as cell proliferation, migration, invasion, apoptosis and angiogenesis. In nearly all these reports, the full-length Ets-1 (p51) is commonly considered to be the active form and the role of the Ets-1?VII splice variant (p42) has not been addressed. Therefore, we studied the functional effects of p42 Ets-1 in comparison to p51 Ets-1 expression in a well-characterized mouse fibroblast cell line. Furthermore, the specific role of Ets-1 was evaluated using mouse fibroblasts with a reduced Ets-1 expression caused by RNAi and compared to fibroblasts with a binding inhibition of the whole ETS transcription factor family by stably overexpressing the ETS DNA binding domain as transdominant-negative mutant. Our results demonstrate that p42 Ets-1 has quite different functions and target genes compared to p51 Ets-1 (e.g. TIMP-4, MMP-3, MMP-9, MMP-13). In some cases (e.g. in cytokine expression) p42 Ets-1 is a functional transcription factor which acts in the same manner as a transdominant-negative approach

Structural insights into the autoregulation and cooperativity of the human transcription factor Ets-2

Ets-2, like its closely related homologue Ets-1, is a member of the Ets family of DNA binding transcription factors. Both proteins are subject to multiple levels of regulation of their DNA binding and transactivation properties. One such regulatory mechanism is the presence of an autoinhibitory module, which in Ets-1 allosterically inhibits the DNA binding activity. This inhibition can be relieved by interaction with protein partners or cooperative binding to closely separated Ets binding sites in a palindromic arrangement. In this study we describe the 2.5 Å resolution crystal structure of a DNA complex of the Ets-2 Ets domain. The Ets domain crystallized with two distinct species in the asymmetric unit, which closely resemble the autoinhibited and DNA bound forms of Ets-1. This discovery prompted us to re-evaluate the current model for the autoinhibitory mechanism and the structural basis for cooperative DNA binding. In contrast to Ets-1, in which the autoinhibition is caused by a combination of allosteric and steric mechanisms, we were unable to find clear evidence for the allosteric mechanism in Ets-2. We also demonstrated two possibly distinct types of cooperative binding to substrates with Ets binding motifs separated by four and six base pairs and suggest possible molecular mechanisms for this behavior

Multinomial goodness-of-fit: large sample tests with survey design correction and exact tests for small samples

A new Stata command called -mgof- is introduced. The command is used to compute distributional tests for discrete (categorical, multinomial) variables. Apart from classic large sample $\chi^2$-approximation tests based on Pearson's $X^2$, the likelihood ratio, or any other statistic from the power-divergence family (Cressie and Read 1984), large sample tests for complex survey designs and exact tests for small samples are supported. The complex survey correction is based on the approach by Rao and Scott (1981) and parallels the survey design correction used for independence tests in -svy:tabulate-. The exact tests are computed using Monte Carlo methods or exhaustive enumeration. An exact Kolmogorov-Smirnov test for discrete data is also provided.multinomial, goodness-of-fit, chi-squared, categorical data, exact tests, Monte Carlo, exhaustive enumeration, combinatorial algorithms, complex survey correction, power-divergence statistic, Kolmogorov-Smirnov, Benford's law

The Intergenerational Transmission of Divorce: A Fifteen-Country Study with the Fertility and Family Survey

Studies mainly from the United States provide evidence that children of divorced parents face a higher risk of divorce in their own marriages. We estimate and analyze the effects of divorce transmission using comparative individual data from the United Nations for 13 eastern and western European countries as well as for Canada and the United States. We find substantial and highly statistically significant transmission effects in all samples. This shows that the intergenerational transmission of divorce is a widespread phenomenon observed without a single exception in our data covering a large number of countries with differing historical, institutional, and cultural contexts.Divorce, Divorce Risk, Intergenerational Transmission, Consequences of Divorce, Child Well-being

Sensitive Questions in Online Surveys: Experimental Results for the Randomized Response Technique (RRT) and the Unmatched Count Technique (UCT)

Gaining valid answers to so-called sensitive questions is an age-old problem in survey research. Various techniques have been developed to guarantee anonymity and minimize the respondent's feelings of jeopardy. Two such techniques are the randomized response technique (RRT) and the unmatched count technique (UCT). In this study we evaluate the effectiveness of different implementations of the RRT (using a forced-response design) in a computer-assisted setting and also compare the use of the RRT to that of the UCT. The techniques are evaluated according to various quality criteria, such as the prevalence estimates they provide, the ease of their use, and respondent trust in the techniques. Our results indicate that the RRTs are problematic with respect to several domains, such as the limited trust they inspire and non-response, and that the RRT estimates are unreliable due to a strong false "no" bias, especially for the more sensitive questions. The UCT, however, performed well compared to the RRTs on all the evaluated measures. The UCT estimates also had more face validity than the RRT estimates. We conclude that the UCT is a promising alternative to RRT in self-administered surveys and that future research should be directed towards evaluating and improving the technique.sensitive questions, online survey, randomized response technique, unmatched count technique, item count technique, methodological experiment

Carbon Trading with Blockchain

Blockchain has the potential to accelerate the deployment of emissions trading systems (ETS) worldwide and improve upon the efficiency of existing systems. In this paper, we present a model for a permissioned blockchain implementation based on the successful European Union (EU) ETS and discuss its potential advantages over existing technology. We propose an ETS model that is both backwards compatible and future-proof, characterised by interconnectedness, transparency, tamper-resistance and high liquidity. Further, we identify key challenges to implementation of a blockchain ETS, as well as areas of future work required to enable a fully-decentralised blockchain ETS

Recent advances in the structural molecular biology of Ets transcription factors: interactions, interfaces and inhibition

The Ets family of eukaryotic transcription factors is based around the conserved Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically and structurally well characterized, structures of homodimeric and ternary complexes point to Ets domains functioning as versatile protein-interaction modules. In the present paper, we review the progress made over the last decade to elucidate the structural mechanisms involved in modulation of DNA binding and protein partner selection during dimerization. We see that Ets domains, although conserved around a core architecture, have evolved to utilize a variety of interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic interfaces for both DNA and protein interaction. Furthermore, we discuss recent advances in drug development for inhibition of Ets factors, and the roles structural biology can play in their future

Environmental tobacco smoke risk perception and smoking behavior in Portugal

This study analyzes public attitudes towards environmental tobacco smoking (ETS) risks. ETS legislation and smoking behaviors using recent data from Special Eurobarometer 272 that is a unique database on public perception of ETS. Some major conclusions are drawn: (1) both smokers and non-smokers are aware of health consequences from ETS, (2) moderate and heavy smokers tend to be less concerned with seriousness of the health consequences, (3) that the belief that ETS increases the risk of a serious disease decreases the probability of being smoker, (4)ETS beliefs do not affect the quitting decision, (5) those who smoke at home appear to be aware of health consequences of ETS, (6) ETS health risk beliefs is negatively associated with the number of cigarette consumed.

Comparative analysis of the existing and proposed ETS

Emissions trading schemes (ETS) have been operational to control greenhouse gas emissions in European Union since 2005. Under the EU ETS, the governments of the Member States agree on national emission caps, allocate allowances to industrial operators, track and validate the actual emissions and retire allowances at the end of each year. ETS have been proposed to be introduced in New Zealand, Australia, Japan, US, Canada, Korea, India and two Chinese provinces in the near future. The main idea of the ETS is to create the market for pollution which will provide economic agents with incentives to reduce their emissions ( Stavins, et al., 2003). The design of ETS plays an important role in reducing greenhouse gas emissions and promoting environmental and economic sustainability. There are several designs of ETS including cap-and-trade, baseline-and-credit and hybrid, however, cap-and-trade scheme is the most popular among the proposed ETS. The purpose of this paper is to perform a comprehensive review of the existing and the proposed ETS focusing on design issues. Findings of this research will be useful for countries with existing and proposed ETS and for countries intending to adopt ETS in the future.Emission Trading Scheme (ETS), Sustainability, Cap-and-trade, Baseline-and-credit, Hybrid

Measurement of environmental tobacco smoke exposure among adults with asthma.

Because the morbidity and mortality from adult asthma have been increasing, the identification of modifiable environmental exposures that exacerbate asthma has become a priority. Limited evidence suggests that exposure to environmental tobacco smoke (ETS) may adversely affect adults with asthma. To study the effects of ETS better, we developed a survey instrument to measure ETS exposure in a cohort of adults with asthma living in northern California, where public indoor smoking is limited. To validate this survey instrument, we used a passive badge monitor that measures actual exposure to ambient nicotine, a direct and specific measure of ETS. In this validation study, we recruited 50 subjects from an ongoing longitudinal asthma cohort study who had a positive screening question for ETS exposure or potential exposure. Each subject wore a passive nicotine badge monitor for 7 days. After the personal monitoring period, we readministered the ETS exposure survey instrument. Based on the survey, self-reported total ETS exposure duration ranged from 0 to 70 hr during the previous 7 days. Based on the upper-range boundary, bars or nightclubs (55 hr) and the home (50 hr) were the sites associated with greatest maximal self-reported exposure. As measured by the personal nicotine badge monitors, the overall median 7-day nicotine concentration was 0.03 microg/m(3) (25th-75th interquartile range 0-3.69 microg/m(3)). Measured nicotine concentrations were highest among persons who reported home exposure (median 0.61 microg/m(3)), followed by work exposure (0.03 microg/m(3)), other (outdoor) exposure (0.025 microg/m(3)), and no exposure (0 microg/m(3); p = 0.03). The Spearman rank correlation coefficient between self-reported ETS exposure duration and directly measured personal nicotine concentration during the same 7-day period was 0.47, supporting the survey's validity (p = 0.0006). Compared to persons with no measured exposure, lower-level [odds ratio (OR) 1.9; 95% confidence interval (CI), 0.4-8.8] and higher-level ETS exposures (OR 6.8; 95% CI, 1.4-32.3) were associated with increased risk of respiratory symptoms. A brief, validated survey instrument can be used to assess ETS exposure among adults with asthma, even with low levels of exposure. This instrument could be a valuable tool for studying the effect of ETS exposure on adult asthma health outcomes