Cellular proteins are decorated with a wide range of acetyl and other acyl modifications. Many studies have demonstrated regulation of site-specific acetylation by acetyltransferases and ...deacetylases. Acylation is emerging as a new type of lysine modification, but less is known about its overall regulatory role. Furthermore, the mechanisms of lysine acylation, its overlap with protein acetylation, and how it influences cellular function are major unanswered questions in the field. In this review, we discuss the known roles of acetyltransferases and deacetylases and the sirtuins as a conserved family of a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacylases that are important for response to cellular stress and homeostasis. We also consider the evidence for an emerging idea of nonenzymatic protein acylation. Finally, we put forward the hypothesis that protein acylation is a form of protein “carbon stress” that the deacylases evolved to remove as a part of a global protein quality-control network.
The sirtuins are protein deacylases that regulate cellular homeostasis and response to stress. In this review, Wagner and Hirschey highlight recent findings on new types of acyl lysine modifications and propose a model for protein acylation as a “carbon stress” that sirtuins remove as part of protein quality control.
Increasing evidence suggests that psychological well-being (PWB) is associated with lower disease and mortality risk, and may be enhanced with relatively low-cost interventions. Yet, dissemination of ...these interventions remains limited, in part because insufficient attention has been paid to distinct PWB dimensions, which may impact physical health outcomes differently.
This essay first reviews the empirical evidence regarding differential relationships between all-cause mortality and multiple dimensions of PWB (e.g., life purpose, mastery, positive affect, life satisfaction, optimism). Then, individual-level positive psychology interventions aimed at increasing PWB and tested in randomized-controlled trials are reviewed as these allow for easy implementation and potentially broad outreach to improve population well-being, in concert with efforts targeting other established social determinants of health.
Several PWB dimensions relate to mortality, with varying strength of evidence. Many of positive psychology trials indicate small-to-moderate improvements in PWB; rigorous institution-level interventions are comparatively few, but preliminary results suggest benefits as well. Examples of existing health policies geared towards the improvement of population well-being are also presented. Future avenues of well-being epidemiological and intervention research, as well as policy implications, are discussed.
Although research in the fields of behavioral and psychosomatic medicine, as well as health psychology have substantially contributed to the science of PWB, this body of work has been somewhat overlooked by the public health community. Yet, the growing interest in documenting well-being, in addition to examining its determinants and consequences at a population level may provoke a shift in perspective. To cultivate optimal well-being-mental, physical, social, and spiritual-consideration of a broader set of well-being measures, rigorous studies, and interventions that can be disseminated is critically needed.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that ...undergo intramolecular catalysis to form reactive intermediates that non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized a protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the "acylomes" of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation and validated malate dehydrogenase as a key target. These data uncover a fundamental relationship between reactive acyl-CoA species and proteins and define a new regulatory paradigm in metabolism.
The US Occupational Safety and Health Administration (OSHA) has not fulfilled its responsibilities in the face of the COVID-19 pandemic. OSHA is then urged to issue an enforceable requirement that ...employers implement measures to decrease COVID-19 incidence among essential workers. The measures are also intended for curbing the spread of the said disease to their families and communities.
The COVID-19 pandemic has highlighted the importance of work in shaping population health and wellbeing. This Viewpoint applies a multilevel systems framework to assist in understanding the diverse ...and complex interactions of forces affecting worker health and wellbeing, and how trending changes in employment and working conditions have been accelerated by the pandemic. Government agencies concerned with population health and wellbeing, and economic activity must expand their capacity to monitor, evaluate, and respond to these trends. In addition, integrated enterprise and workplace-based approaches that consider the interactions among these multidimensional drivers will build organisation and worker resilience to navigate the continual changes in work and worker safety, health, and wellbeing in a post-pandemic world.
Thriving from Work is a construct that has been highlighted as an important integrative positive worker well-being indicator that can be used in both research and practice. Recent public discourse ...emphasizes the important contributions that work should have on workers' lives in positive and meaningful ways and the importance of valid and reliable instruments to measure worker well-being. The Thriving from Work Questionnaire measures how workers' experiences of their work and conditions of work contributes in positive ways to their thriving both at and outside of work.
The purpose of this study was to translate the Thriving from Work Questionnaire from English to Spanish, and then validate the translated questionnaire in a sample of 8,795 finance workers in Peru and Mexico. We used item response theory models replicating methods that were used for the original validation studies. We conducted a differential item functioning analysis to evaluate any differences in the performance of models between Peru and Mexico. We evaluated criterion validity with organizational leadership, flourishing, vitality, community well-being, and worker's home location socio-economic position.
The current study demonstrates that the Spanish (Peru/Mexico) questionnaire was found to be a reliable and valid measure of workers' thriving from work. One item was dropped from the long-form version of the original U.S. questionnaire. Both the long and short form versions of the questionnaire had similar psychometric properties. Empirical reliability was high. Criterion validity was established as hypothesized relationships between constructs was supported. There were no differences in the performance of the model between countries suggesting utility across Latin American countries.
The current study demonstrated that the Spanish (Peru and Mexico) version of the questionnaire is both a reliable and valid measure of worker well-being in Latin America. Specific recommendations are made for the adaptation of the questionnaire and directions of future research.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The childhood heart disease of Friedreich's Ataxia (FRDA) is characterized by hypertrophy and failure. It is caused by loss of frataxin (FXN), a mitochondrial protein involved in energy homeostasis. ...FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity. Protein acetylation is an important regulator of cardiac metabolism and loss of SIRT3 increases susceptibility of the heart to stress-induced cardiac hypertrophy and ischemic injury. The underlying pathophysiology of heart failure in FRDA is unclear. The purpose of this study was to examine in detail the physiologic and acetylation changes of the heart that occur over time in a model of FRDA heart failure. We predicted that increased mitochondrial protein acetylation would be associated with a decrease in heart function in a model of FRDA.
A conditional mouse model of FRDA cardiomyopathy with ablation of FXN (FXN KO) in the heart was compared to healthy controls at postnatal days 30, 45 and 65. We evaluated hearts using echocardiography, cardiac catheterization, histology, protein acetylation and expression.
Acetylation was temporally progressive and paralleled evolution of heart failure in the FXN KO model. Increased acetylation preceded detectable abnormalities in cardiac function and progressed rapidly with age in the FXN KO mouse. Acetylation was also associated with cardiac fibrosis, mitochondrial damage, impaired fat metabolism, and diastolic and systolic dysfunction leading to heart failure. There was a strong inverse correlation between level of protein acetylation and heart function.
These results demonstrate a close relationship between mitochondrial protein acetylation, physiologic dysfunction and metabolic disruption in FRDA hypertrophic cardiomyopathy and suggest that abnormal acetylation contributes to the pathophysiology of heart disease in FRDA. Mitochondrial protein acetylation may represent a therapeutic target for early intervention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The mechanisms initiating protein acylation in mitochondria are unknown.
Results: The pH and acyl-CoA concentrations of the mitochondrial matrix are sufficient to cause protein lysine acetylation and ...succinylation.
Conclusion: Protein acylation in mitochondria may be a nonenzymatic event facilitated by the alkaline pH and high acyl-CoA concentrations.
Significance: The mitochondrial deacylases SIRT3 and SIRT5 may have evolved to regulate nonenzymatic protein acylation.
Alterations in mitochondrial protein acetylation are implicated in the pathophysiology of diabetes, the metabolic syndrome, mitochondrial disorders, and cancer. However, a viable mechanism responsible for the widespread acetylation in mitochondria remains unknown. Here, we demonstrate that the physiologic pH and acyl-CoA concentrations of the mitochondrial matrix are sufficient to cause dose- and time-dependent, but enzyme-independent acetylation and succinylation of mitochondrial and nonmitochondrial proteins in vitro. These data suggest that protein acylation in mitochondria may be a chemical event facilitated by the alkaline pH and high concentrations of reactive acyl-CoAs present in the mitochondrial matrix. Although these results do not exclude the possibility of enzyme-mediated protein acylation in mitochondria, they demonstrate that such a mechanism may not be required in its unique chemical environment. These findings may have implications for the evolutionary roles that the mitochondria-localized SIRT3 deacetylase and SIRT5 desuccinylase have in the maintenance of metabolic health.
Many organizational interventions aim to improve working conditions to promote and protect worker safety, health, and well-being. The Workplace Organizational Health Study used process evaluation to ...examine factors influencing implementation of an organizational intervention. This paper examines the extent to which the intervention was implemented as planned, the dose of intervention implemented, and ways the organizational context hindered or facilitated the implementation of the intervention.
This proof-of-concept trial was conducted with a large, multinational company that provides food service through contractual arrangements with corporate clients. The 13-month intervention was launched in five intervention sites in October 2018. We report findings on intervention implementation based on process tracking and qualitative data. Qualitative data from 25 post-intervention interviews and 89 process tracking documents were coded and thematically analyzed.
Over the 13-month intervention, research team representatives met with site managers monthly to provide consultation and technical assistance on safety and ergonomics, work intensity, and job enrichment. Approximately two-thirds of the planned in-person or phone contacts occurred. We tailored the intervention to each site as we learned more about context, work demands, and relationships. The research team additionally met regularly with senior leadership and district managers, who provided corporate resources and guidance. By assessing the context of the food service setting in which the intervention was situated, we explored factors hindering and facilitating the implementation of the intervention. The financial pressures, competing priorities and the fast-paced work environment placed constraints on site managers' availability and limited the full implementation of the intervention.
Despite strong support from corporate senior leadership, we encountered barriers in the implementation of the planned intervention at the worksite and district levels. These included financial demands that drove work intensity; turnover of site and district managers disrupting continuity in the implementation of the intervention; and staffing constraints that further increased the work load and pace. Findings underscore the need for ongoing commitment and support from both the parent employer and the host client.
This study was retrospectively registered with the Clinical Trials. Gov Protocol and Results System on June 2, 2021 with assigned registration number NCT04913168 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This Viewpoint examines some of the missteps during the COVID-19 pandemic to protect health care workers and how to use lessons from those mistakes for future pandemics.
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