Sexual maturation must occur on a controlled developmental schedule. In mammals, Makorin3 (MKRN3) and the miRNA regulators LIN28A/B are key regulators of this process, but how they act is unclear. In C. elegans, sexual maturation of the nervous system includes the functional remodeling of postmitotic neurons and the onset of adult-specific behaviors. Here, we find that the lin-28–let-7 axis (the ‘heterochronic pathway’) determines the timing of these events. Upstream of lin-28, the Makorin lep-2 and the lncRNA lep-5 regulate maturation cell-autonomously, indicating that distributed clocks, not a central timer, coordinate sexual differentiation of the C. elegans nervous system. Overexpression of human MKRN3 delays aspects of C. elegans sexual maturation, suggesting the conservation of Makorin function. These studies reveal roles for a Makorin and a lncRNA in timing of sexual differentiation; moreover, they demonstrate deep conservation of the lin-28–let-7 system in controlling the functional maturation of the nervous system.

Highlights d lep-5 acts in the heterochronic pathway to promote the larvalto-adult transition d lep-5 is a 600 nt, highly structured lncRNA that is conserved across Caenorhabditis d Like the Makorin LEP-2, lep-5 promotes the degradation of LIN-28 protein d lep-5 may act as a scaffold to bring LEP-2 into close proximity with LIN-28

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Ephrins, the Eph family of receptor tyrosine kinases and their ligands, have been shown to be key players in guiding cell migration, polarization, and cell‐matrix and cell‐cell adhesions. Specifically, the ligand Ephrin‐A1 has been shown to regulate cell motility and morphology through the activation of EphA receptors, which signal to PI3K pathway to induce cell contraction. We performed live cell experiments on mouse embryonic fibroblasts (MEFs) to study the interrelations of molecular activation of myosin light‐chain kinase (MLCK) as determined by fluorescence resonance energy transfer (FRET), mechanical tension as measured by using novel 3D intracellular force microscopy (3D IFM), and cell morphology in response to Ephrin‐A1. The results demonstrate positive correlations among the elevation of MLCK, an increase in intracellular mechanical tension, and a reduction of cell area, which indicates an augmentation of contraction. These effects of Ephrin‐A1 were absent in MEFs with PI3K subunit p85b knockout (p85b‐/‐), indicating that p85b in PI3K plays a significant role in mediating the chemical, mechanical, and morphological effects of Ephrine‐A1. This study serves to elucidate the mechano‐chemical regulation of cell dynamics under Ephrine‐A1 guidance. Grant Funding Source: Supported by NIH HL108375 (Shu Chien), NSF: (Shaochen Chen)

Enhancements of a building integrated photovoltaic/thermal (BIPV/T) system intended for coupling with an air source multispeed heat pump (MSHP) is presented. The systems were analyzed using a modified version of EnergyPlus, a quasi-steady state building energy simulation program. A sensitivity analysis of the internal channel surface and cover emissivity parameters of the Opaque BIPV/T, transparent BIPV/T, and building integrated solar air heater collectors (BISAH) was conducted. In addition, collector arrangement analyses were performed. A BIPV/T- BISAH array design was selected based on the results of the analyses and evaluated using a net-zero energy house and an energy efficient house. The integrated BIPV/T-BISAH coupled ASHP system reduced space heating electricity consumption of the net-zero house by 6.5% and the energy efficient house by 3.4%. These low levels of savings were largely due to the passive design of the houses that reduced heating loads during sunny hours; this resulted in a mismatch between the hours when the integrated system could provide energy savings and the need for space heating.