905 resultados para post-translational regulation


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The financial crisis of 2007–2009 and the resultant pressures exerted on policymakers to prevent future crises have precipitated coordinated regulatory responses globally. A key focus of the new wave of regulation is to ensure the removal of practices now deemed problematic with new controls for conducting transactions and maintaining holdings. There is increasing pressure on organizations to retire manual processes and adopt core systems, such as Investment Management Systems (IMS). These systems facilitate trading and ensure transactions are compliant by transcribing regulatory requirements into automated rules and applying them to trades. The motivation of this study is to explore the extent to which such systems may enable the alteration of previously embedded practices. We researched implementations of an IMS at eight global financial organizations and found that overall the IMS encourages responsible trading through surveillance, monitoring and the automation of regulatory rules and that such systems are likely to become further embedded within financial organizations. We found evidence that some older practices persisted. Our study suggests that the institutionalization of technology-induced compliant behaviour is still uncertain.

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Objective To investigate the effect of nutrient stimulation of gut hormones by oligofructose supplementation on appetite, energy intake (EI), body weight (BW) and adiposity in overweight and obese volunteers. Methods In a parallel, single-blind and placebo-controlled study, 22 healthy overweight and obese volunteers were randomly allocated to receive 30 g day−1 oligofructose or cellulose for 6 weeks following a 2-week run-in. Subjective appetite and side effect scores, breath hydrogen, serum short chain fatty acids (SCFAs), plasma gut hormones, glucose and insulin concentrations, EI, BW and adiposity were quantified at baseline and post-supplementation. Results Oligofructose increased breath hydrogen (P < 0.0001), late acetate concentrations (P = 0.024), tended to increase total area under the curve (tAUC)420mins peptide YY (PYY) (P = 0.056) and reduced tAUC450mins hunger (P = 0.034) and motivation to eat (P = 0.013) when compared with cellulose. However, there was no significant difference between the groups in other parameters although within group analyses showed an increase in glucagon-like peptide 1 (GLP-1) (P = 0.006) in the cellulose group and a decrease in EI during ad libitum meal in both groups. Conclusions Oligofructose increased plasma PYY concentrations and suppressed appetite, while cellulose increased GLP-1 concentrations. EI decreased in both groups. However, these positive effects did not translate into changes in BW or adiposity.

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Activating transcription factor 3 (Atf3) is rapidly and transiently upregulated in numerous systems, and is associated with various disease states. Atf3 is required for negative feedback regulation of other genes, but is itself subject to negative feedback regulation possibly by autorepression. In cardiomyocytes, Atf3 and Egr1 mRNAs are upregulated via ERK1/2 signalling and Atf3 suppresses Egr1 expression. We previously developed a mathematical model for the Atf3-Egr1 system. Here, we adjusted and extended the model to explore mechanisms of Atf3 feedback regulation. Introduction of an autorepressive loop for Atf3 tuned down its expression and inhibition of Egr1 was lost, demonstrating that negative feedback regulation of Atf3 by Atf3 itself is implausible in this context. Experimentally, signals downstream from ERK1/2 suppress Atf3 expression. Mathematical modelling indicated that this cannot occur by phosphorylation of pre-existing inhibitory transcriptional regulators because the time delay is too short. De novo synthesis of an inhibitory transcription factor (ITF) with a high affinity for the Atf3 promoter could suppress Atf3 expression, but (as with the Atf3 autorepression loop) inhibition of Egr1 was lost. Developing the model to include newly-synthesised miRNAs very efficiently terminated Atf3 protein expression and, with a 4-fold increase in the rate of degradation of mRNA from the mRNA/miRNA complex, profiles for Atf3 mRNA, Atf3 protein and Egr1 mRNA approximated to the experimental data. Combining the ITF model with that of the miRNA did not improve the profiles suggesting that miRNAs are likely to play a dominant role in switching off Atf3 expression post-induction.

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Based on a large dataset from eight Asian economies, we test the impact of post-crisis regulatory reforms on the performance of depository institutions in countries at different levels of financial development. We allow for technological heterogeneity and estimate a set of country-level stochastic cost frontiers followed by a deterministic bootstrapped meta-frontier to evaluate cost efficiency and cost technology. Our results support the view that liberalization policies have a positive impact on bank performance, while the reverse is true for prudential regulation policies. The removal of activities restrictions, bank privatization and foreign bank entry have a positive and significant impact on technological progress and cost efficiency. In contrast, prudential policies, which aim to protect the banking sector from excessive risk-taking, tend to adversely affect banks cost efficiency but not cost technology.

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Muscle glycogen is an important fuel for contracting skeletal muscle during prolonged strenuous exercise, and glycogen depletion has been implicated in muscle fatigue. It is also apparent that glycogen availability can exert important effects on a range of metabolic and cellular processes. These processes include carbohydrate, fat and protein metabolism during exercise, post-exercise glycogen resynthesis, excitation–contraction coupling, insulin action and gene transcription. For example, low muscle glycogen is associated with reduced muscle glycogenolysis, increased glucose and NEFA uptake and protein degradation, accelerated glycogen resynthesis, impaired excitation–contraction coupling, enhanced insulin action and potentiation of the exercise-induced increases in transcription of metabolic genes. Future studies should identify the mechanisms underlying, and the functional importance of, the association between glycogen availability and these processes.

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Recovery after prolonged or high-intensity exercise is characterised by a substantial increase in adipose tissue lipolysis, resulting in elevated rates of plasma-derived fat oxidation. Despite the large increase in circulating fatty acids (FAs) after exercise, only a small fraction of this is taken up by exercised muscle in the lower extremities. Indeed, the predominant fate of non-oxidised FAs derived from post-exercise lipolysis is reesteriflcation hi the liver. During recovery from endurance exercise, a number of changes also occur hi skeletal muscle that allow for a high metabolic priority towards glycogen resynthesis. Reducing muscle glycogen during exercise potentiates these effects, however the cellular and molecular mechanisms regulating substrate oxidation following exercise remain poorly defined. The broad arm of this thesis was to examine the regulation of fat metabolism during recovery from glycogen-lowering exercise hi the presence of altered fat and glucose availability. In study I, eight endurance-trained males completed a bout of exhaustive exercise followed by ingestion of carbohydrate (CHO)-rich meals (64-70% of energy from CHO) at 1, 4, and 7 h of recovery. Duplicate muscle biopsies were obtained at exhaustion and 3, 6 and 18 h of recovery. Despite the large intake of CHO during recovery (491 ± 28 g or 6.8 + 0.3 g • kg-1), respiratory exchange ratio values of 0.77 to 0.84 indicated a greater reliance on fat as an oxidative fuel. Intramuscular triacylglycerol (IMTG) content remained unchanged in the presence of elevated glucose and insulin levels during recovery , suggesting IMTG has a negligible role in contributing to the enhanced fat oxidation after exhaustive exercise. It appears that the partitioning of exogenous glucose towards glycogen resynthesis is of high metabolic priority during immediate post-exercise recovery, supported by the trend towards reduced pyruvate dehydrogenase (PDH) activity and increased fat oxidation. The effect of altering plasma FA availability during post-exercise recovery was examined in study II. Eight endurance-trained males performed three trials consisting of glycogen-lowering exercise, followed by infusion of either saline (CON), saline + nicotinic acid (NA) (LFA) or Intralipid and heparin (HFA). Muscle biopsies were obtained at the end of exercise (0 h) and at 3 and 6 h in recovery. Altering the availability of plasma FAs during recovery induced changes in whole-body fat oxidation that were unrelated to differences in skeletal muscle malonyl-CoA. Furthermore, fat oxidation and acetyl-CoA carboxylase (ACC) phosphorylation appear to be dissociated after exercise, suggesting mechanisms other than phosphorylation-mediated changes in ACC activity have an important role in regulating malonyl-CoA and fat metabolism in human skeletal muscle after exercise. Alternative mechanisms include citrate and long-chain fatty acyl-CoA mediated changes in ACC activity, or differences in malonyl-CoA decarboxylase (MCD) activity. Reducing plasma FA concentrations with NA attenuated the post-exercise increase in MCD and pyruvate dehydrogenase kinase 4 (PDK4) gene expression, suggesting that FAs and/or other factors induced by NA are involved hi the regulation of these genes. Despite marked changes hi plasma FA availability, no significant changes in IMTG concentration were detected, providing further evidence that plasma-derived FAs are the preferential fuel source contributing to the enhanced fat oxidation post-exercise during recovery. To further examine the effect of substrate availability after exercise, Study III investigated the regulation of fat metabolism during a 6 h recovery period with or without glucose infusion. Enhanced glucose availability significantly increased CHO oxidation compared with the fasted state, although no differences in whole-body fat oxidation were apparent. Consistent with the similar rates of fat metabolism, no difference hi AMPK or ACCβ phosphorylation were observed between trials. In addition, no significant treatment or time effects for IMTG concentration were detected during recovery. The large exercise-induced PDK4 gene expression was attenuated when plasma FAs were reduced during glucose infusion, supporting the hypothesis that PDK4 is responsive to sustained changes in lipid availability and/or changes in plasma insulin. Furthermore, the possibility exists that the suppression of PDK4 mRNA also reduced PDK activity and thus maintained PDH activity to account for the higher rates of CHO oxidation observed during glucose infusion compared with the control trial.

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Judging time-to-contact with a target is an important criterion for avoiding harm in everyday walking and running tasks, and maximizing performance in high-velocity sporting tasks. The information-based regulation of step length and duration during target-directed locomotion was examined in relation to gait mode, approach velocity, target task, expertise, and sporting performance during a series of four experiments. The first three experiments examined novice performers (Each n=12, 6 males, 6 females), whilst the last experiment examined expert gymnasts (n=5). Two reference strips with alternating 50cm black and white intervals were placed on either side of the approach strip for all of the experiments. One 50Hz-panning video camera filmed the approach from an elevated position. In Experiment 4, two stationary 250Hz cameras filmed the post-flight performance of the gymnastic vaults and, in addition, two qualified judges provided a performance score for each vaulting trial. The panning video footage in each experiment was digitized to deduce the gait characteristics. In Experiment 4, the high-speed video footage was analyzed three-dimensionally to obtain the performance measures such as post-flight height. The utilization of visual stimulus in target-directed locomotion is affected by the observer's state of motion as characterized by the mode of locomotion and also often the speed of locomotion. In addition, experience plays an important role in the capacity of the observer to utilize visual stimulus to control the muscular action of locomotion when either maintaining or adjusting the step mechanics. The characteristics of the terrain and the target also affect the observer's movement. Visual regulation of step length decreases at higher approach speeds in novice performers, where as expert performers are capable of increasing visual regulation at higher approach speeds. Conservatism in final foot placement by female participants accounts for the observed increase in distance from the critical boundary of the obstacle relative to toe placement. Behavioural effects of gender thus affect the control of final foot placement in obstacle-directed locomotion. The visual control of braking in target-directed locomotion is described by a tau-dot of-0.54. When tau-dot is below -0.54 a hard collision with the obstacle will occur, however, when tau-dot is above -0.54, a soft collision with the target will occur. It is suggested that the tau-dot margin defining the control of braking reveals the braking capacity of the system. In the target-directed locomotion examined a tau-dot greater than -0.70 would possibly exceed the braking capacity of the system, thus, leading to injury if performed. The approach towards the take-off board and vaulting horse in gymnastics is an example of target-directed locomotion in sport. Increased visual regulation of the timing and length of each step is a requirement for a fast running approach, a fundamental building block for the execution of complex vaults in gymnastics. The successful performance of complex vaults in gymnastics leads towards a higher judge's score. Future research suggestions include an investigation of visual regulation of step length in curved target-directed locomotion.

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Purpose – The purpose of this paper is to provide an overarching conceptual decision model that delineates the major issues and decisions associated with carbon regulations that will allow executives to better understand the potential regulatory schemes and implications that may be imposed in the near future.
Design/methodology/approach – The authors use the extant literature as the foundation to develop a conceptual model of the decisions pertaining to climate change regulation that face business executives today.
Findings – This paper suggests four major categories of issues that must be addressed in any climate change regulatory scheme. These include: “scope” – will carbon emission management systems be global or regional; “who pays” – will the consumer or will the supply chain be responsible for the cost of their emissions; “market or compliance-based mechanisms” – will the CO2 emissions system be market-based or a compliance-based regulatory system; and “criteria” – how can credence of the remedy be established – what is necessary for a business initiative to qualify for as a creditable carbon offset?
Research limitations/implications – This paper offers a framework that categories the fundamental decisions that must be made in any climate change regulation. This framework may be useful in advancing research into any of the four categories of decisions and their implications on commerce and the environment. This paper is designed to be managerially useful and in that way does limit its ability to specifically advance many dimensions of research.
Practical implications – The paper offers executives for a simple model of the decisions that must be made to craft an effective climate change regulatory scheme. In addition, it suggests how these decisions may create exploitable economic opportunities for innovative and proactive firms.
Originality/value – This paper adds value to the debate by clarifying the decisions that must be addressed in any climate change regulation scheme.

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The aims of this study were to examine (a) the effects of competition-related and competition-extraneous concerns on affective states; (b) the relationships of primary and secondary appraisal with affective states and (c) the main and moderating effects of personality traits on pre- and post-competition affects. Thirty-nine male elite martial artists were assessed on 12 affective states, concerns and dimensions of primary and secondary appraisal at five random times a day across 1 week before and 3 days after a competition. On the competition day, they were assessed 1 h before and immediately after the contest. Competitive trait anxiety, neuroticism and extraversion were measured at the start of the study. The competition was the most significant and stressful event experienced in the examined period and had a pervasive influence on athletes' affective states. All examined appraisal and personality factors were somewhat associated with pre- and post-competition affective states. Competitive trait anxiety was a key moderator of the relationship between cognitive appraisal and affective states. This study supports the idea that cognitive appraisal and situational and personality factors exert main and interactive effects on athletes' pre- and post-competition affects. These factors need to be accounted for in planning of emotion regulation interventions.

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The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P= 0.04), miR-31 and HDAC4 protein (r =-0.87; P= 0.026) and miR-31 and NRF1 protein (r =-0.77; P= 0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3′ untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health

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Granulocyte-Colony Stimulating Factor (G-CSF) is a commercially available drug with research linking it to favourable muscle adaptations, post trauma. Molecular techniques were used to identify the G-CSF receptor in skeletal muscle and G-CSF treatment was used to determine the molecular mechanisms by which G-CSF enhances muscle growth and regeneration.

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 The incidence of insulin resistance and type 2 diabetes (T2D) is increasing at alarming rates. In the quest to understand the underlying causes of and to identify novel therapeutic targets to treat T2D, scientists have become increasingly reliant on the use of rodent models. Here, we provide a discussion on the regulation of rodent glucose metabolism, highlighting key differences and similarities that exist between rodents and humans. In addition, some of the issues and considerations associated with assessing glucose homeostasis and insulin action are outlined. We also discuss the role of the liver vs. skeletal muscle in regulating whole body glucose metabolism in rodents, emphasizing the importance of defective hepatic glucose metabolism in the development of impaired glucose tolerance, insulin resistance, and T2D. © 2014 the American Physiological Society.

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Background: Given the rising rates of obesity in children and adolescents, developing evidence-based weight loss or weight maintenance interventions that can be widely disseminated, well implemented, and are highly scalable is a public health necessity. Such interventions should ensure that adolescents establish healthy weight regulation practices while also reducing eating disorder risk.

Objective:
This study describes an online program, StayingFit, which has two tracks for universal and targeted delivery and was designed to enhance healthy living skills, encourage healthy weight regulation, and improve weight/shape concerns among high school adolescents.

Methods:
Ninth grade students in two high schools in the San Francisco Bay area and in St Louis were invited to participate. Students who were overweight (body mass index [BMI] >85th percentile) were offered the weight management track of StayingFit; students who were normal weight were offered the healthy habits track. The 12-session program included a monitored discussion group and interactive self-monitoring logs. Measures completed pre- and post-intervention included self-report height and weight, used to calculate BMI percentile for age and sex and standardized BMI (zBMI), Youth Risk Behavior Survey (YRBS) nutrition data, the Weight Concerns Scale, and the Center for Epidemiological Studies Depression Scale.

Results: A total of 336 students provided informed consent and were included in the analyses. The racial breakdown of the sample was as follows: 46.7% (157/336) multiracial/other, 31.0% (104/336) Caucasian, 16.7% (56/336) African American, and 5.7% (19/336) did not specify; 43.5% (146/336) of students identified as Hispanic/Latino. BMI percentile and zBMI significantly decreased among students in the weight management track. BMI percentile and zBMI did not significantly change among students in the healthy habits track, demonstrating that these students maintained their weight. Weight/shape concerns significantly decreased among participants in both tracks who had elevated weight/shape concerns at baseline. Fruit and vegetable consumption increased for both tracks. Physical activity increased among participants in the weight management track, while soda consumption and television time decreased.

Conclusions: Results suggest that an Internet-based, universally delivered, targeted intervention may support healthy weight regulation, improve weight/shape concerns among participants with eating disorders risk, and increase physical activity in high school students. Tailored content and interactive features to encourage behavior change may lead to sustainable improvements in adolescent health.

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The striated muscle activator of Rho signaling (STARS) protein and members of its downstream signaling pathway, including myocardin-related transcription factor-A (MRTF-A) and SRF, are increased in response to prolonged resistance exercise training but also following a single bout of endurance cycling. The aim of the present study was to measure and compare the regulation of STARS, MRTF-A and SRF mRNA and protein following 10 weeks of endurance training (ET) versus resistance training (RT), as well as before and following a single bout of endurance (EE) versus resistance exercise (RE). Following prolonged training, STARS, MRTF-A and SRF mRNA levels were all increased by similar magnitude, irrespective of training type. In the training-habituated state, STARS mRNA increased following a single-bout RE when measured 2.5 and 5 h post-exercise and had returned to resting level by 22 h following exercise. MRTF-A and SRF mRNA levels were decreased by 2.5, 5, and 22 h following a single bout of RE and EE exercise when compared to their respective basal levels, with no significant difference seen between the groups at any of the time points. No changes in protein levels were observed following the two modes of exercise training or a single bout of exercise. This study demonstrates that the stress signals elicited by ET and RT result in a comparable regulation of members of the STARS pathway. In contrast, a single bout of EE and RE, performed in the trained state, elicit different responses. These observations suggest that in the trained state, the acute regulation of the STARS pathway following EE or RE may be responsible for exercise-specific muscle adaptations.