Epithelial-to-mesenchymal stem cell transition in a human organ: Lessons from Lichen Planopilaris

YesEpithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles, during the inflammatory permanent alopecia, lichen planopilaris. We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with transforming growth factor-β1, epidermal growth factor, and IFN-γ administration, which to our knowledge has not been reported previously. Moreover, induction of EMT within primary human eSCs can be prevented and even partially reversed ex vivo by peroxisome proliferator−activated receptor-γ agonists, likely through suppression of the transforming growth factor-β signaling pathway. Furthermore, we show that peroxisome proliferator−activated receptor-γ agonists also attenuates the EMT signature even in lesional lichen planopilaris hair follicles ex vivo. We introduce lichen planopilaris as a model disease for pathological EMT in human adult eSCs, report a preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ, and show that peroxisome proliferator−activated receptor-γ agonists are promising agents for suppressing and partially reversing EMT in human hair follicles eSCs ex vivo, including in lichen planopilaris

Molecular Dynamics Simulation of the M2 Helices within the Nicotinic Acetylcholine Receptor Transmembrane Domain: Structure and Collective Motions

Multiple nanosecond duration molecular dynamics simulations were performed on the transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were free to move, whereas the outer (M1, M3, M4) helix bundle was backbone restrained. The M2 helices largely retain their hydrogen-bonding pattern throughout the simulation, with some distortions in the helical end and loop regions. All of the M2 helices exhibit bending motions, with the hinge point in the vicinity of the central hydrophobic gate region (corresponding to residues αL251 and αV255). The bending motions of the M2 helices lead to a degree of dynamic narrowing of the pore in the region of the proposed hydrophobic gate. Calculations of Born energy profiles for various structures along the simulation trajectory suggest that the conformations of the M2 bundle sampled correspond to a closed conformation of the channel. Principal components analyses of each of the M2 helices, and of the five-helix M2 bundle, reveal concerted motions that may be relevant to channel function. Normal mode analyses using the anisotropic network model reveal collective motions similar to those identified by principal components analyses

Proceedings of International Web Conference in Civil Engineering for a Sustainable Planet

This proceeding contains articles of the various research ideas of the academic community and practitioners accepted at the "International Web Conference in Civil Engineering for a Sustainable Planet (ICCESP 2021)". ICCESP 2021 is being Organized by the Habilete Learning Solutions, Kollam in Collaboration with American Society of Civil Engineers (ASCE), TKM College of Engineering, Kollam, and Baselios Mathews II College of Engineering, Kollam, Kerala, India. Conference Title: International Web Conference in Civil Engineering for a Sustainable PlanetConference Acronym: ICCESP 2021Conference Date: 05–06 March 2021Conference Location: Online (Virtual Mode)Conference Organizer: Habilete Learning Solutions, Kollam, Kerala, IndiaCollaborators: American Society of Civil Engineers (ASCE), TKM College of Engineering, Kollam, and Baselios Mathews II College of Engineering, Kollam, Kerala, India