38 research outputs found
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Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts
Reprogramming somatic cells from one cell fate to another can generate specific neurons suitable for disease modeling. To maximize the utility of patient-derived neurons, they must model not only disease-relevant cell classes but also the diversity of neuronal subtypes found in vivo and the pathophysiological changes that underlie specific clinical diseases. Here, we identify five transcription factors that reprogram mouse and human fibroblasts into noxious stimulus-detecting (nociceptor) neurons that recapitulate the expression of quintessential nociceptor-specific functional receptors and channels found in adult mouse nociceptor neurons as well as native subtype diversity. Moreover, the derived nociceptor neurons exhibit TrpV1 sensitization to the inflammatory mediator prostaglandin E2 and the chemotherapeutic drug oxaliplatin, modeling the inherent mechanisms underlying inflammatory pain hypersensitivity and painful chemotherapy-induced neuropathy. Using fibroblasts from patients with familial dysautonomia (hereditary sensory and autonomic neuropathy type III), we show that the technique can reveal novel aspects of human disease phenotypes in vitro
Synthesis of Fluorinated Segment Containing Oligomers for Supercritical CO2 Applications
Syntheses of various fluorine-based surfactants, namely fluorinated-segment-containing block co-oligomers, were achieved by the radical polymerization of mainly acrylate-based monomers. These types of surfactants serve as stabilizers for supercritical carbon dioxide (scCO2) media based applications, for which the effective solubilization of materials in the supercritical phase is generally not possible because of solubility problems faced when CO2 is involved. Initially, a difunctional fluorinated initiator was synthesized in two steps. First, 4,4-azobis-4-cyanovaleric acid was chlorinated with SOCl2, and then the product, 4,4-azobis-4-cyanovaleryl chloride, was reacted with a fluorinated alcohol to obtain the initiator for the polymerization reactions. The synthesized triblock co-oligomers consisted of fluorinated side blocks and a hydrocarbon intermediate block. Efficient solubilization of the materials in scCO2 was observed. It was experimentally shown that the solubility efficiency was affected by specific interactions between CO2 and the oligomers, and these were determined by the nature and size of the inner block and by the chain length of the fluorinated side blocks in comparison with the inner block