scholarly journals Epigenetic Drifts during Long-Term Intestinal Organoid Culture

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1718
Author(s):  
Torsten Thalheim ◽  
Susann Siebert ◽  
Marianne Quaas ◽  
Maria Herberg ◽  
Michal R. Schweiger ◽  
...  
Keyword(s):  
Gene Activation ◽  
Growth Conditions ◽  
Dna Demethylation ◽  
Metabolic Adaptation ◽  
Long Term Culture ◽  
Organoid Culture ◽  
Transcriptional Changes ◽  
Tissue Of Origin ◽  
And Control

Organoids retain the morphological and molecular patterns of their tissue of origin, are self-organizing, relatively simple to handle and accessible to genetic engineering. Thus, they represent an optimal tool for studying the mechanisms of tissue maintenance and aging. Long-term expansion under standard growth conditions, however, is accompanied by changes in the growth pattern and kinetics. As a potential explanation of these alterations, epigenetic drifts in organoid culture have been suggested. Here, we studied histone tri-methylation at lysine 4 (H3K4me3) and 27 (H3K27me3) and transcriptome profiles of intestinal organoids derived from mismatch repair (MMR)-deficient and control mice and cultured for 3 and 20 weeks and compared them with data on their tissue of origin. We found that, besides the expected changes in short-term culture, the organoids showed profound changes in their epigenomes also during the long-term culture. The most prominent were epigenetic gene activation by H3K4me3 recruitment to previously unmodified genes and by H3K27me3 loss from originally bivalent genes. We showed that a long-term culture is linked to broad transcriptional changes that indicate an ongoing maturation and metabolic adaptation process. This process was disturbed in MMR-deficient mice, resulting in endoplasmic reticulum (ER) stress and Wnt activation. Our results can be explained in terms of a mathematical model assuming that epigenetic changes during a long-term culture involve DNA demethylation that ceases if the metabolic adaptation is disturbed.

Suppressed, but Not Forgotten

2011 ◽  
Vol 70 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Beat Meier ◽  
Anja König ◽  
Samuel Parak ◽  
Katharina Henke
Keyword(s):  
Memory Trace ◽  
Thought Suppression ◽  
Test Phase ◽  
Indirect Test ◽  
Final Test ◽  
Test Experiment ◽  
And Control ◽  
Cue Words ◽  
The Impact

This study investigates the impact of thought suppression over a 1-week interval. In two experiments with 80 university students each, we used the think/no-think paradigm in which participants initially learn a list of word pairs (cue-target associations). Then they were presented with some of the cue words again and should either respond with the target word or avoid thinking about it. In the final test phase, their memory for the initially learned cue-target pairs was tested. In Experiment 1, type of memory test was manipulated (i.e., direct vs. indirect). In Experiment 2, type of no-think instructions was manipulated (i.e., suppress vs. substitute). Overall, our results showed poorer memory for no-think and control items compared to think items across all experiments and conditions. Critically, however, more no-think than control items were remembered after the 1-week interval in the direct, but not in the indirect test (Experiment 1) and with thought suppression, but not thought substitution instructions (Experiment 2). We suggest that during thought suppression a brief reactivation of the learned association may lead to reconsolidation of the memory trace and hence to better retrieval of suppressed than control items in the long term.

Strengthening of occupational health promotion by the German Prevention Health Care Act

2019 ◽  
pp. 188-190
Author(s):  
Diana Hart
Keyword(s):  
Public Health ◽  
Health Care ◽  
Health Promotion ◽  
Primary Prevention ◽  
Occupational Health ◽  
Life Expectancy ◽  
Prevention And Control ◽  
Occupational Health Promotion ◽  
And Control

All countries are faced with the problem of the prevention and control of non-communicable diseases (NCD): implement prevention strategies eff ectively, keep up the momentum with long term benefi ts at the individual and the population level, at the same time tackling hea lth inequalities. Th e aff ordability of therapy and care including innovative therapies is going to be one of the key public health priorities in the years to come. Germany has taken in the prevention and control of NCDs. Germany’s health system has a long history of guaranteeing access to high-quality treatment through universal health care coverage. Th r ough their membership people are entitled to prevention and care services maintaining and restoring their health as well as long term follow-up. Like in many other countries general life expectancy has been increasing steadily in Germany. Currently, the average life expectancy is 83 and 79 years in women and men, respectively. Th e other side of the coin is that population aging is strongly associated with a growing burden of disease from NCDs. Already over 70 percent of all deaths in Germany are caused by four disease entities: cardiovascular disease, cancer, chronic respiratory disease and diabetes. Th ese diseases all share four common risk factors: smoking, alcohol abuse, lack of physical activity and overweight. At the same time, more and more people become long term survivors of disease due to improved therapy and care. Th e German Government and public health decision makers are aware of the need for action and have responded by initiating and implementing a wide spectrum of activities. One instrument by strengthening primary prevention is the Prevention Health Care Act. Its overarching aim is to prevent NCDs before they can manifest themselves by strengthening primary prevention and health promotion in diff erent sett ings. One of the main emphasis of the Prevention Health Care Act is the occupational health promotion at the workplace.

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