The EMC complex, a highly conserved transmembrane chaperone in the endoplasmic reticulum (ER), has been associated in humans with sterol homeostasis and a myriad of different cellular activities, rendering the mechanism of EMC functionality enigmatic. Using fission yeast, we demonstrate that the EMC complex facilitates the biogenesis of the sterol transfer protein Lam6/Ltc1 at ER-plasma membrane and ER-mitochondria contact sites. Cells that lose EMC function sequester unfolded Lam6/Ltc1 and other proteins at the mitochondrial matrix, leading to surplus ergosterol, cold-sensitive growth, and mitochondrial dysfunctions. Remarkably, inhibition of ergosterol biosynthesis, but also fluidization of cell membranes to counteract their rigidizing effects, reduce the ER-unfolded protein response and rescue growth and mitochondrial defects in EMC-deficient cells. These results suggest that EMC-assisted biogenesis of Lam6/Ltc1 may provide, through ergosterol homeostasis, optimal membrane fluidity to facilitate biogenesis of other ER-membrane proteins.

The basal forebrain (BF) cholinergic system (BFCS) participates in functions that are global across the brain, such as sleep-wake cycles, but also participates in capacities that are more behaviorally and anatomically specific, including sensory perception. However, how it orchestrates all the diverse local and global functions remains to be understood. To uncover the underlying organization principles, we combined data from rat brains by tracing projections from the BF to cortical areas and analyzed spatial-numerical relations of neurons to their cortical targets. The combined dataset revealed algorithmically identified and hierarchically organized three principal networks: somatosensory-motor, auditory, and visual, as defined by the sensory modality most predominant within them. These clusters of cholinergic neurons could enable the BFCS to coordinate spatially selective signaling, including the parallel modulation of multiple functionally interconnected yet diverse groups of cortical areas. This previously unseen blueprint of the hierarchy of cholinergic clusters is ready for functional testing.

Understanding how morphogen gradients spatially pattern tissues is a fundamental question in developmental biology but can be difficult to directly address using conventional approaches. Here, we expose hPSC-derived endoderm cells to countervailing gradients of anteriorizing and posteriorizing signals using a widely available microfluidic device. This approach yielded spatially patterned cultures comprising anterior foregut (precursor to the thyroid, esophagus, and lungs) and mid/hindgut (precursor to the intestines) cells, whose identities were confirmed using single-cell RNA sequencing (scRNA-seq). By exposing stem cells to externally applied signaling gradients, this widely accessible microfluidic platform should accelerate the production of spatially patterned tissues, complementing internally self-organizing organoids. Applying artificial morphogen gradients invitro may also illuminate how developing tissues interpret signaling gradients in systems that are not readily accessible for in vivo studies.

Developing moist-electric array device using screen printing technology that meets mass customization, high power output, and wearable capabilities is very attractive for sustainable mobile power. However, the design of sandwich stacked moist-electric array devices and their screen printing patterning manufacturing process are still challenging. Here, we developed a large-scale fine construction strategy for ion diode nano-channels compatible with screen printing process. A single moist-electric device can generate an open circuit voltage of 0.7V and a short circuit current density of 56.69μA/cm2. After large-area integrated manufacturing, the array can generate an open circuit voltage of 126V and a short circuit current of 5.47 mA. In addition, compared with the spraying process, the performance deviation between different array units is greatly reduced using the screen printing process, which is the key to ensuring the application of moist-electric technology from a single prototype device to a functional integrated device.