Detection of sequential polyubiquitylation on a millisecond timescale

The pathway by which ubiquitin chains are generated on substrate through a cascade of enzymes consisting of an E1, E2 and E3 remains unclear. Multiple distinct models involving chain assembly on E2 or substrate have been proposed. However, the speed and complexity of the reaction have precluded direct experimental tests to distinguish between potential pathways. Here we introduce new theoretical and experimental methodologies to address both limitations. A quantitative framework based on product distribution predicts that the really interesting new gene (RING) E3 enzymes SCF^(Cdc4) and SCF^(β-TrCP) work with the E2 Cdc34 to build polyubiquitin chains on substrates by sequential transfers of single ubiquitins. Measurements with millisecond time resolution directly demonstrate that substrate polyubiquitylation proceeds sequentially. Our results present an unprecedented glimpse into the mechanism of RING ubiquitin ligases and illuminate the quantitative parameters that underlie the rate and pattern of ubiquitin chain assembly

Asymmetry in Resting Alpha Activity: Effects of Handedness

Frontal electroencephalographic (EEG) alpha band power during rest shows increased right, and/or decreased left, hemisphere activity under conditions of state or trait withdrawal-associated effect. Non-right-handers (NRH) are more likely to have mental illnesses and dispositions that involve such withdrawal-related effect. The aim of the study was to examine whether NRH might be characterized by increased right, relative to left, hemisphere activity during rest. Methods: The present research investigated that hypothesis by examining resting EEG alpha power in consistently-right-handed (CRH) and NRH individuals. Results: In support of the hypothesis, NRH demonstrated decreased right hemisphere alpha power, and therefore increased right hemisphere activity, during rest, compared to CRH.Conclusions: The study demonstrates further support for an association between increased right hemisphere activity and negative affect via an association between such EEG activity and NRH

Why People Are Not Willing to Let Their Children Ride in Driverless School Buses: A Gender and Nationality Comparison

As driverless vehicles proliferate, it is possible that this technology will be applied in mass transport vehicles. School buses may be suited for autonomous operations as they follow set routes and schedules. However, a research gap exists in whether or not parents would be willing to have their children ride in autonomously operated school buses. The purpose of this study was to examine parents’ willingness to allow their child to ride in an autonomous school bus. Participant gender and nationality were also two independent variables, along with affect measures as a possible mediating variable. The research used a two-study approach. In study one, it was found that participants were less willing to have their child ride in a driverless school bus than a traditional human-operated vehicle. In study two, findings suggest a significant interaction between the type of driver, participant gender, and nationality. In general, American females were less willing than Indian females and overall, Americans were less willing than Indians in the driverless conditions. Affect was found to be a mediating variable, which suggests that emotions were playing a role in the responses of participants. The paper concludes with theoretical contributions, practical applications, and suggestions for future research

Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study

BACKGROUND: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome. METHODS: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pao2) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pao2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pao2 and poor neurological outcome. To assess whether there was an association between other supranormal Pao2 levels and poor neurological outcome, we used other Pao2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg). RESULTS: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1-23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11-1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02-1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg. CONCLUSIONS: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge

Embodied truths: How dynamic gestures and speech contribute to mathematical proof practices

Grounded and embodied theories of cognition suggest that both language and the body play crucial roles in grounding higher-order thought. This paper investigates how particular forms of speech and gesture function together to support abstract thought in mathematical proof construction. We use computerized text analysis software to evaluate how speech patterns support valid proof construction for two different tasks, and we use gesture analysis to investigate how dynamic gestures—those gestures that depict and transform mathematical objects—further support proof practices above and beyond speech patterns. We also evaluate the degree to which speech and gesture convey distinct information about mathematical reasoning during proving. Dynamic gestures and speech indicating logical inference support valid proof construction, and both dynamic gestures and speech uniquely predict variance in valid proof construction. Thus, dynamic gestures and speech each make separate and important contributions to the formulation of mathematical arguments, and both modalities can convey elements of students’ understanding to teachers and researchers

A Preliminary Comparison of Pilots\u27 Weather Minimums and Actual Decision-Making

Adverse weather conditions remain a leading contributing factor in general aviation accidents. In compromising situations, such as severe weather, pilots continue to make decisions, which endanger themselves, passengers, and the aircraft. Although technology and training have lowered the risks associated with poor decision making by aviators, they are often still faced with scenarios requiring split second judgments. A countermeasure to these risks is the use of personal weather minimums by pilots. The purpose of this study was to examine pilot’s decision-making and performance, while flying an instrument approach, under extreme conditions of low visibility and ceiling as based on their stated personal minimums. A sample of 35 flight students with instrument ratings was recruited from a large university flight program located in the southeastern part of the United States. Participants were asked a series of pre-test questions, including their personal weather minimums, and then flew an ILS instrument approach on an Elite-1000 flight simulator at the subject university. The findings indicate approximately eighty percent of participants, on average, descended nearly two-hundred feet below their stated personal minimums before aborting the approach. Furthermore, forty percent of them also flew twenty-five feet below the federal requirement (200 feet above ground level) before aborting the approach. These results are pertinent to advance our understanding of the many different variables affecting pilot’s decision making. Understanding these outcomes will progress our initiatives to ensure safer air travel, while improving pilot’s competence and their passenger’s confidence

Cand1 Promotes Assembly of New SCF Complexes through Dynamic Exchange of F Box Proteins

The modular SCF (Skp1, cullin, and F box) ubiquitin ligases feature a large family of F box protein substrate receptors that enable recognition of diverse targets. However, how the repertoire of SCF complexes is sustained remains unclear. Real-time measurements of formation and disassembly indicate that SCF^(Fbxw7) is extraordinarily stable, but, in the Nedd8-deconjugated state, the cullin-binding protein Cand1 augments its dissociation by one-million-fold. Binding and ubiquitylation assays show that Cand1 is a protein exchange factor that accelerates the rate at which Cul1-Rbx1 equilibrates with multiple F box protein-Skp1 modules. Depletion of Cand1 from cells impedes recruitment of new F box proteins to pre-existing Cul1 and profoundly alters the cellular landscape of SCF complexes. We suggest that catalyzed protein exchange may be a general feature of dynamic macromolecular machines and propose a hypothesis for how substrates, Nedd8, and Cand1 collaborate to regulate the cellular repertoire of SCF complexes

Evaluation of the use of Global Youth Tobacco Survey (GYTS) data for developing evidence-based tobacco control policies in Turkey

Introduction The tobacco control effort in Turkey has made significant progress in recent years. Turkey initiated its tobacco control effort with the passing of Law 4207 (The Prevention of Harmful Effects of Tobacco Products) in 1996 and ratified the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) in 2004. It is important to base policy decisions on valid and reliable evidence from population-based, representative studies that are periodically repeated to enable policy makers to monitor the results of their interventions and to appropriately tailor anti-tobacco activities towards future needs. Methods The Global Youth Tobacco Survey (GYTS) was developed to track tobacco use among young people and enhance the capacity of countries to design, implement, and evaluate tobacco control and prevention programs. Turkey conducted the GYTS in 2003 and data from this survey can be used as baseline measures for evaluation of the tobacco control programs implemented by the Ministry of Health (MOH) of the Turkish government. Results The GYTS was conducted in 2003 on a representative sample of students aged 13 to 15 years. It indicated that almost 3 in 10 students in Turkey had ever smoked cigarettes, with significantly higher rates among boys. Current cigarette smoking rates were lower, at 9% for boys and 4% for girls. The prevalence of current use of other tobacco products was about half these figures for each gender. About 80% were exposed to secondhand smoke. Exposure to pro-smoking media messages was not rare. Almost half of the smokers 'usually' bought their tobacco from a store, despite the law prohibiting this. Exposure to teaching against smoking in schools was not universal. Conclusion Findings from the GYTS, with periodic repeats of the survey, can be used to monitor the impact of enforcing various provisions of the present law (No: 4207), the progress made in achieving the goals of the WHO FCTC, and the effectiveness of various preventive interventions against smoking. Such data would inform and help in the development of public health strategy.PubMedWoSScopu

Tobacco use among students aged 13–15 years in Greece: the GYTS project

BACKGROUND: Data on the prevalence of tobacco use among teenagers in Greece are limited. We examined the prevalence of smoking among middle-school students in Greece using the Global Youth Tobacco Survey (GYTS). METHODS: The Global Youth Tobacco Survey was implemented in Greece during the academic year 2004 – 2005 by the University of Thessaly and the National School of Public Health. Data were collected using the GYTS self-administered anonymous questionnaire, which was distributed by specifically trained field workers to a nationally representative sample of middle-school students aged 13–15 years (through randomly selected schools and classes), randomly selected through a two-stage cluster sample design. Data processing and statistical analyses were performed at the Centers for Disease Control and Prevention (CDC). RESULTS: About one third of the students 32.1% (29.4 – 35.0) reported that they had tried tobacco in the past, while 16.2% (14.3 – 18.4) reported being current users of tobacco products. In addition, 1 in 4 of ever smokers reported that they began smoking before the age of 10 years old. Almost 1 in 5 never smokers reported being susceptible to initiate smoking in the next year and about 89.8% (88.3 – 91.1) of the respondents were exposed to environmental tobacco smoke in their homes and 94.1% (93.2 – 94.9) in public places. Finally, a strikingly high number of students 95% (89.5 – 97.7) reported that they were able to buy their own cigarettes without restrictions. CONCLUSION: The results of the GYTS show that the prevalence of smoking in middle-school children is alarmingly high in Greece. Smoking among young people constitutes a significant problem that is destined to worsen in the absence of any comprehensive efforts focused on strict anti-smoking legislation, policies and tobacco control interventions targeting children at a young age

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500