Vesicles driven by dynein and kinesin exhibit directional reversals without regulators.

Intracellular vesicular transport along cytoskeletal filaments ensures targeted cargo delivery. Such transport is rarely unidirectional but rather bidirectional, with frequent directional reversals owing to the simultaneous presence of opposite-polarity motors. So far, it has been unclear whether such complex motility pattern results from the sole mechanical interplay between opposite-polarity motors or requires regulators. Here, we demonstrate that a minimal system, comprising purified Dynein-Dynactin-BICD2 (DDB) and kinesin-3 (KIF16B) attached to large unilamellar vesicles, faithfully reproduces in vivo cargo motility, including runs, pauses, and reversals. Remarkably, opposing motors do not affect vesicle velocity during runs. Our computational model reveals that the engagement of a small number of motors is pivotal for transitioning between runs and pauses. Taken together, our results suggest that motors bound to vesicular cargo transiently engage in a tug-of-war during pauses. Subsequently, stochastic motor attachment and detachment events can lead to directional reversals without the need for regulators.

The Impact of Sex, Body Mass Index, Age, Exercise Type and Exercise Duration on Interstitial Glucose Levels during Exercise.

The impact of age, sex and body mass index on interstitial glucose levels as measured via continuous glucose monitoring (CGM) during exercise in the healthy population is largely unexplored. We conducted a multivariable generalized estimating equation (GEE) analysis on CGM data (Dexcom G6, 10 days) collected from 119 healthy exercising individuals using CGM with the following specified covariates: age; sex; BMI; exercise type and duration. Females had lower postexercise glycemia as compared with males (92 ± 18 vs. 100 ± 20 mg/dL, p = 0.04) and a greater change in glycemia during exercise from pre- to postexercise (p = 0.001) or from pre-exercise to glucose nadir during exercise (p = 0.009). Younger individuals (i.e., <20 yrs) had higher glucose during exercise as compared with all other age groups (all p < 0.05) and less CGM data in the hypoglycemic range (<70 mg/dL) as compared with those aged 20-39 yrs (p < 0.05). Those who were underweight, based on body mass index (BMI: <18.5 kg/m2), had higher pre-exercise glycemia than the healthy BMI group (104 ± 20 vs. 97 ± 17 mg/dL, p = 0.02) but similar glucose levels after exercise. Resistance exercise was associated with less of a drop in glycemia as compared with aerobic or mixed forms of exercise (p = 0.008) and resulted in a lower percent of time in the hypoglycemic (p = 0.04) or hyperglycemic (glucose > 140 mg/dL) (p = 0.03) ranges. In summary, various factors such as age, sex and exercise type appear to have subtle but potentially important influence on CGM measurements during exercise in healthy individuals.