bioRxiv ScienceSearch

Biology subjects

McAuley, E.

Publications and source records attributed to McAuley, E..

2 recordsLinked to original sources

Resting State Functional Connectivity Predicts Future Changes in Sedentary Behavior

Information about a persons available energy resources is integrated in daily behavioral choices that weigh motor costs against expected rewards. It has been posited that humans have an innate attraction towards effort minimization and that executive control is required to overcome this prepotent disposition. With sedentary behaviors increasing at the cost of millions of dollars spent in health care and productivity losses due to physical inactivity-related deaths, understanding the predictors of sedentary behaviors will improve future intervention development and precision medicine approaches. In 64 healthy older adults participating in a 6-month aerobic exercise intervention, we use neuroimaging (resting state functional connectivity), baseline measures of executive function and accelerometer measures of time spent sedentary to predict future changes in objectively measured time spent sedentary in daily life. Using cross-validation and bootstrap resampling, our results demonstrate that functional connectivity between 1) the anterior cingulate cortex and the supplementary motor area and 2) the right anterior insula and the left temporoparietal/temporooccipital junction, predict changes in time spent sedentary, whereas baseline cognitive, behavioral and demographic measures do not. Previous research has shown activation in and between the anterior cingulate and supplementary motor area as well as in the right anterior insula during effort avoidance and tasks that integrate motor costs and reward benefits in effort-based decision making. Our results add important knowledge toward understanding mechanistic associations underlying complex sedentary behaviors.

neuroscience

Rate volatility and asymmetric segregation diversify mutation burden in mutator cells.

Mutations that compromise mismatch repair (MMR) or DNA polymerase exonuclease domains produce mutator phenotypes capable of fueling cancer evolution. Tandem defects in these pathways dramatically increase mutation rate. Here, we model how mutator phenotypes expand genetic heterogeneity in budding yeast cells using a single-cell resolution approach that tallies all replication errors arising from individual divisions. The distribution of count data from cells lacking MMR and polymerase proofreading was broader than expected for a single rate, consistent with volatility of the mutator phenotype. The number of mismatches that segregated to the mother and daughter cells after the initial round of replication co-varied, suggesting that mutagenesis in each division is governed by a different underlying rate. The distribution of "fixed" mutation counts that cells inherit is further broadened by an unequal sharing of mutations due to semiconservative replication and Mendelian segregation. Modeling suggests that this asymmetric segregation may diversify mutation burden in mutator-driven tumors.

cancer biology