A Non-Canonical E-Box Within the \u3cem\u3eMyoD\u3c/em\u3e Core Enhancer is Necessary for Circadian Expression in Skeletal Muscle

The myogenic differentiation 1 (MyoD) gene is a master regulator of myogenesis. We previously reported that the expression of MyoD mRNA oscillates over 24 h in skeletal muscle and that the circadian clock transcription factors, BMAL1 (brain and muscle ARNT-like 1) and CLOCK (circadian locomotor output cycles kaput), were bound to the core enhancer (CE) of the MyoD gene in vivo. In this study, we provide in vivo and in vitro evidence that the CE is necessary for circadian expression of MyoD in adult muscle. Gel shift assays identified a conserved non-canonical E-box within the CE that is bound by CLOCK and BMAL1. Functional analysis revealed that this E-box was required for full activation by BMAL1/CLOCK and for in vitro circadian oscillation. Expression profiling of muscle of CEloxP/loxP mice found approximately 1300 genes mis-expressed relative to wild-type. Based on the informatics results, we analyzed the respiratory function of mitochondria isolated from wild-type and CEloxP/loxP mice. These assays determined that State 5 respiration was significantly reduced in CEloxP/loxP muscle. The results of this work identify a novel element in the MyoD enhancer that confers circadian regulation to MyoD in skeletal muscle and suggest that loss of circadian regulation leads to changes in myogenic expression and downstream mitochondrial function

A non-canonical E-box within the MyoD core enhancer is necessary for circadian expression in skeletal muscle

The myogenic differentiation 1 (MyoD) gene is a master regulator of myogenesis. We previously reported that the expression of MyoD mRNA oscillates over 24 h in skeletal muscle and that the circadian clock transcription factors, BMAL1 (brain and muscle ARNT-like 1) and CLOCK (circadian locomotor output cycles kaput), were bound to the core enhancer (CE) of the MyoD gene in vivo. In this study, we provide in vivo and in vitro evidence that the CE is necessary for circadian expression of MyoD in adult muscle. Gel shift assays identified a conserved non-canonical E-box within the CE that is bound by CLOCK and BMAL1. Functional analysis revealed that this E-box was required for full activation by BMAL1/CLOCK and for in vitro circadian oscillation. Expression profiling of muscle of CEloxP/loxP mice found approximately 1300 genes mis-expressed relative to wild-type. Based on the informatics results, we analyzed the respiratory function of mitochondria isolated from wild-type and CEloxP/loxP mice. These assays determined that State 5 respiration was significantly reduced in CEloxP/loxP muscle. The results of this work identify a novel element in the MyoD enhancer that confers circadian regulation to MyoD in skeletal muscle and suggest that loss of circadian regulation leads to changes in myogenic expression and downstream mitochondrial function

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

What is Donald Trump?:Forms of 'Celebrity' in Celebrity Politics

It is widely assumed that Donald Trump is a ‘celebrity politician’, and that he has cashed in his success on the reality show The Apprentice to secure political credibility and attention. In this respect he fits what Matthew Wood et al (2016) have labelled the ‘superstar celebrity politician’. This characterisation is the latest in a number of refinements to the definition and understanding of the celebrity politician. While this is a helpful move, I want to suggest that it might overlook one key dimension of the phenomenon. Definitions of the celebrity politician tend to focus on the source of their ‘celebrity’ – how they became famous, rather than on how they act out their celebrity role. This latter dimension features in media coverage, where journalists and commentators borrow from showbusiness to describe politics, but is less often analysed in the political science literature. It matters because, I want to suggest, celebrity politicians like Trump act as stars, whether of reality television, rock music or film. They do not just resemble stars; they are them. This is evident in how they are represented, how they perform and how their ‘fans’ respond to them. It is also symptomatic of wider changes in the conduct and form of the contemporary, mediatised political realm

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Leadership and style in the French Fifth Republic:Nicolas Sarkozy’s presidency in historical and cultural perspective

This article contributes to the body of the developing theoretical research in leadership and presidential studies by adding analysis of what I have termed ‘comportmental style’ as a factor in leader/follower relations. Within institutionalism and the wider structure/agency debate in political science, one of the challenges as regards the study of leadership is to identify factors that offer scope to or else militate against leaders’ performance. The comportmental style of Nicolas Sarkozy (President of the French Republic 2007–2012), deployed in the context of the – changing – institution of the presidency, was a major factor in his extreme unpopularity, and contributed to his defeat in 2012. What this tells us about the nature of the changing French presidency and the role of style will be discussed in the conclusion

Collisional and Radiative Processes in Optically Thin Plasmas

Most of our knowledge of the physical processes in distant plasmas is obtained through measurement of the radiation they produce. Here we provide an overview of the main collisional and radiative processes and examples of diagnostics relevant to the microphysical processes in the plasma. Many analyses assume a time-steady plasma with ion populations in equilibrium with the local temperature and Maxwellian distributions of particle velocities, but these assumptions are easily violated in many cases. We consider these departures from equilibrium and possible diagnostics in detail