Structural and functional dissection of the Pacinian corpuscle reveals an active role of the inner core in touch detection.

Pacinian corpuscles are rapidly adapting mechanoreceptor end-organs that detect transient touch and high-frequency vibration. In the prevailing model, these properties are determined by the outer core, which acts as a mechanical filter limiting static and low-frequency stimuli from reaching the afferent terminal-the sole site of touch detection in corpuscles. Here, we determine the detailed 3D architecture of corpuscular components and reveal their contribution to touch detection.

The Integrated Stress Response in Pancreatic Development, Tissue Homeostasis, and Cancer.

Present in all eukaryotic cells, the integrated stress response (ISR) is a highly coordinated signaling network that controls cellular behavior, metabolism, and survival in response to diverse stresses. The ISR is initiated when any 1 of 4 stress-sensing kinases (protein kinase R-like endoplasmic reticulum kinase [PERK], general control non-derepressible 2 [GCN2], double-stranded RNA-dependent protein kinase [PKR], heme-regulated eukaryotic translation initiation factor 2α kinase [HRI]) becomes activated to phosphorylate the protein translation initiation factor eukaryotic translation initiation factor 2α (eIF2α), shifting gene expression toward a comprehensive rewiring of cellular machinery to promote adaptation. Although the ISR has been shown to play an important role in the homeostasis of multiple tissues, evidence suggests that it is particularly crucial for the development and ongoing health of the pancreas.

Effects of Complete and Partial Loss of the 24S-Hydroxycholesterol-Generating Enzyme on Behavior and Hippocampal Transcription in Mouse.

Brain cholesterol metabolic products include neurosteroids and oxysterols, which play important roles in cellular physiology. In neurons, the cholesterol oxidation product, 24S-hydroxycholesterol (24S-HC), is a regulator of signaling and transcription. Here, we examined the behavioral effects of 24S-HC loss, using global and cell-selective genetic deletion of the synthetic enzyme CYP46A1.

3D architecture and a bicellular mechanism of touch detection in mechanosensory corpuscle.

Mechanosensory corpuscles detect transient touch and vibration in the skin of vertebrates, enabling precise sensation of the physical environment. The corpuscle contains a mechanoreceptor afferent surrounded by lamellar cells (LCs), but corpuscular ultrastructure and the role of LCs in touch detection are unknown. We report the three-dimensional architecture of the avian Meissner (Grandry) corpuscle acquired using enhanced focused ion beam scanning electron microscopy and machine learning-based segmentation.