Calcium supplementation for the prevention of hypertensive disorders of pregnancy: current evidence and programmatic considerations.

Most low- and middle-income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500-mg doses/day). WHO recommends 1.5-2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low-dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost-effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron-containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food-based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation.

Cargo rigidity affects the sensitivity of dynein ensembles to individual motor pausing.

Cytoplasmic dynein is a minus-end directed microtubule-based motor protein that drives intracellular cargo transport in eukaryotic cells. Although many intracellular cargos are propelled by small groups of dynein motors, the biophysical mechanisms governing ensemble motility remain largely unknown. To investigate the emergent motility of motor ensembles, we have designed a programmable DNA origami synthetic cargo "chassis" enabling us to control the number of dynein motors in the ensemble and vary the rigidity of the cargo chassis itself. Using total internal reflection fluorescence microscopy, we have observed dynein ensembles transporting these cargo chassis along microtubules in vitro. We find that ensemble motility depends on cargo rigidity: as the number of motors increases, ensembles transporting flexible cargos move comparatively faster than a single motor, whereas ensembles transporting rigid cargos move slower than a single motor. To explain this, we show that ensembles connected through flexible cargos are less sensitive to the pauses of individual motors within the ensemble. We conclude that cargo rigidity plays an important role in communicating and coordinating the states of motors, and consequently in the subsequent mechanisms of collective motility. The insensitivity of ensemble-driven cargos to the pausing of individual motors may contribute to the robustness and versatility of intracellular cargo transport. © 2016 Wiley Periodicals, Inc.