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Creators/Authors contains: "Cheng, Philip"

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  1. ; ; ; ; ; ; ; ; ; ; et al ( , Sleep)
    Abstract Study Objectives

    Examine the ability of a physiologically based mathematical model of human circadian rhythms to predict circadian phase, as measured by salivary dim light melatonin onset (DLMO), in children compared to other proxy measurements of circadian phase (bedtime, sleep midpoint, and wake time).

     Methods

    As part of an ongoing clinical trial, a sample of 29 elementary school children (mean age: 7.4 ± .97 years) completed 7 days of wrist actigraphy before a lab visit to assess DLMO. Hourly salivary melatonin samples were collected under dim light conditions (<5 lx). Data from actigraphy were used to generate predictions of circadian phase using both a physiologically based circadian limit cycle oscillator mathematical model (Hannay model), and published regression equations that utilize average sleep onset, midpoint, and offset to predict DLMO. Agreement of proxy predictions with measured DLMO were assessed and compared.

     Results

    DLMO predictions using the Hannay model outperformed DLMO predictions based on children’s sleep/wake parameters with a Lin’s Concordance Correlation Coefficient (LinCCC) of 0.79 compared to 0.41–0.59 for sleep/wake parameters. The mean absolute error was 31 min for the Hannay model compared to 35–38 min for the sleep/wake variables.

     Conclusion

    Our findings suggest that sleep/wake behaviors were weak proxies of DLMO phase in children, but mathematical models using data collected from wearable data can be used to improve the accuracy of those predictions. Additional research is needed to better adapt these adult models for use in children.

     Clinical Trial

    The i Heart Rhythm Project: Healthy Sleep and Behavioral Rhythms for Obesity Prevention https://clinicaltrials.gov/ct2/show/NCT04445740.

     
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  2. ; ; ; ; ( , Obesity)
    <sc>A</sc>bstract Objective

    This study examined the validity of a novel metric of circadian health, the Entrainment Signal Regularity Index (ESRI), and its relationship to changes in BMI during the school year and summer.

     Methods

    In a longitudinal observational data set, this study examined the relationship between ESRI score and children's (n = 119, 5‐ to 8‐year‐olds) sleep and physical activity levels during the school year and summer, differences in ESRI score during the school year and summer, and the association of ESRI score during the school year and summer with changes in BMI across those time periods.

     Results

    The ESRI score was higher during the school year (0.70 ± 0.10) compared with summer (0.63 ± 0.11);t(111) = 5.484,p < 0.001. Whereas the ESRI score at the beginning of the school year did not significantly predict BMI change during the school year (β = 0.05 ± 0.09 SE,p = 0.57), having a higher ESRI score during summer predicted smaller increases in BMI during summer (β = −0.22 ± 0.10 SE,p = 0.03).

     Conclusions

    Overall, children demonstrated higher entrainment regularity during the school year compared with the summer. During summer, having a higher entrainment signal was associated with smaller changes in summertime BMI. This effect was independent of the effects of children's sleep midpoint, sleep regularity, and physical activity on children's BMI.

     
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  3. ; ; ; ; ; ; ; ; ( , Sleep)
    null (Ed.)
    Abstract From smart work scheduling to optimal drug timing, there is enormous potential in translating circadian rhythms research results for precision medicine in the real world. However, the pursuit of such effort requires the ability to accurately estimate circadian phase outside of the laboratory. One approach is to predict circadian phase noninvasively using light and activity measurements and mathematical models of the human circadian clock. Most mathematical models take light as an input and predict the effect of light on the human circadian system. However, consumer-grade wearables that are already owned by millions of individuals record activity instead of light, which prompts an evaluation of the accuracy of predicting circadian phase using motion alone. Here, we evaluate the ability of four different models of the human circadian clock to estimate circadian phase from data acquired by wrist-worn wearable devices. Multiple datasets across populations with varying degrees of circadian disruption were used for generalizability. Though the models we test yield similar predictions, analysis of data from 27 shift workers with high levels of circadian disruption shows that activity, which is recorded in almost every wearable device, is better at predicting circadian phase than measured light levels from wrist-worn devices when processed by mathematical models. In those living under normal living conditions, circadian phase can typically be predicted to within 1 h, even with data from a widely available commercial device (the Apple Watch). These results show that circadian phase can be predicted using existing data passively collected by millions of individuals with comparable accuracy to much more invasive and expensive methods. 
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  4. ; ; ; ; ; ; ; ; ; ; et al ( , Genetics)
    Bomblies, K (Ed.)
    Abstract Much of the visual diversity of angiosperms is due to the frequent evolution of novel pigmentation patterns in flowers. The gene network responsible for anthocyanin pigmentation, in particular, has become a model for investigating how genetic changes give rise to phenotypic innovation. In the monkeyflower genus Mimulus, an evolutionarily recent gain of petal lobe anthocyanin pigmentation in M. luteus var. variegatus was previously mapped to genomic region pla2. Here, we use sequence and expression analysis, followed by transgenic manipulation of gene expression, to identify MYB5a—orthologous to the NEGAN transcriptional activator from M. lewisii—as the gene responsible for the transition to anthocyanin-pigmented petals in M. l. variegatus. In other monkeyflower taxa, MYB5a/NEGAN is part of a reaction-diffusion network that produces semi-repeating spotting patterns, such as the array of spots in the nectar guides of both M. lewisii and M. guttatus. Its co-option for the evolution of an apparently non-patterned trait—the solid petal lobe pigmentation of M. l. variegatus—illustrates how reaction-diffusion can contribute to evolutionary novelty in non-obvious ways. Transcriptome sequencing of a MYB5a RNAi line of M. l. variegatus reveals that this genetically simple change, which we hypothesize to be a regulatory mutation in cis to MYB5a, has cascading effects on gene expression, not only on the enzyme-encoding genes traditionally thought of as the targets of MYB5a but also on all of its known partners in the anthocyanin regulatory network. 
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