Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild.DOI:
http://dx.doi.org/10.7554/eLife.17670.001
Our findings suggest that uncontrolled age differences between famine and post-famine births could explain most effects commonly attributed to the famine. For more reliable estimates of long-term famine effects in China, other analyses will be needed with age-appropriate controls and better information on the severity and timing of the famine in the populations included.
Background
In C. elegans, germline development and early embryogenesis rely on post-transcriptional regulation of maternally transcribed mRNAs. In many cases, the 3′UTR is sufficient to govern the expression patterns of these transcripts. Several RNA-binding proteins are required to regulate maternal mRNAs through the 3′UTR. Despite intensive efforts to map RNA-binding protein-mRNA interactions in vivo, the biological impact of most binding events remains unknown. Reporter studies using single copy integrated transgenes are essential to evaluate the functional consequences of interactions between RNA-binding proteins and their associated mRNAs.
Results
In this report, we present an efficient method of generating reporter strains with improved throughput by using a library variant of MosSCI transgenesis. Furthermore, using RNA interference, we identify the suite of RBPs that control the expression pattern of five different maternal mRNAs.
Conclusions
The results provide a generalizable and efficient strategy to assess the functional relevance of protein-RNA interactions in vivo, and reveal new regulatory connections between key RNA-binding proteins and their maternal mRNA targets.
Background
There has been a limited recognition of hypertension and diabetes in China which has compromised optimal treatment. It is not clear if a screening program implemented by a national health survey has improved awareness and management of these conditions.
Methods
The China Health and Retirement Longitudinal Study (CHARLS) is an ongoing longitudinal health survey conducted since 2011 among Chinese people aged 45 years and older. Participants have been assessed every two years by interviews, physical examinations, and fasting glucose samples were taken in 2011. In 2013 and 2015, participants were asked about awareness and management of selected chronic diseases, and they first became aware of these conditions.
Results
Of the 11,000+ participants screened in 2011, 4594 were identified with hypertension and 1703 with diabetes by medical examinations. Over 80% of the middle-aged and elderly Chinese diagnosed with hypertension and/or diabetes in 2011 reported in 2015 that they were unaware of the disease(s). Although some improvement was observed between 2011 and 2015, the main reason for the increase in awareness was a medical examination initiated by the study participant (over 75%), by their work unit or community (12–15%), and rarely (less than 3%) by the CHARLS examination. Participants with a rural household registration status and lower BMI were the most likely to be unaware and to remain unaware of their condition(s).
Conclusions
Disease screening in CHARLS did not lead to significant improvements in awareness of hypertension and diabetes. Improvements should be made by the systematic feedback of screening results to survey participants and the monitoring of disease awareness over time. This will be essential to improve disease recognition and facilitate optimal management.
Electronic supplementary material
The online version of this article (10.1186/s12889-019-6753-x) contains supplementary material, which is available to authorized users.
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