Overexpression of Cys2His2 zinc-finger 322A (ZNF322A) oncogenic transcription factor is associated with lung tumorigenesis. However, the mechanism of ZNF322A overexpression remains poorly understood. Here, we discover that protein stability of ZNF322A is regulated by coordinated phosphorylation and ubiquitination through the CK1δ/GSK3β/FBXW7α axis. CK1δ and GSK3β kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7α leading to ZNF322A protein destruction. Overexpression of FBXW7α induces ZNF322A protein degradation, thereby blocks ZNF322A transcription activity and suppresses ZNF322A-induced tumor growth and metastasis in vitro and in vivo. Clinically, overexpression of ZNF322A correlates with low FBXW7α or defective CK1δ/GSK3β-mediated phosphorylation in lung cancer patients. Multivariate Cox regression analysis indicates that patients with ZNF322A high/FBXW7 low expression profile can be used as an independent factor to predict the clinical outcome in lung cancer patients. Our results reveal a new mechanism of ZNF322A oncoprotein destruction regulated by the CK1δ/GSK3β/FBXW7α axis. Deregulation of this signaling axis results in ZNF322A overexpression and promotes cancer progression.
This paper investigates the intense airglow brightness often observed in the 630.0 nm limb images taken using Imager of Sprites and Upper Atmospheric Lightnings (ISUAL), onboard FORMOSAT-2 satellite, where the tangent plane of the measurement falls in the local midnight sector. Most of the images show only single brightness, but in some cases there could be multiple peaks, which sometimes appears to be centered on geographic equator and in some cases falls on either sides of the magnetic equator. In order to understand such intense emission in the near-midnight hours, the observations are simulated using SAMI2 (SAMI2 is Another Model of the Ionosphere) model parameters based on the ISUAL viewing geometry. The simulations reproduced the measured airglow intensity pattern quite remarkably and suggested that the meridional neutral wind and the resulting plasma distribution are closely related with the observed brightness. The intensity and locations of the airglow brightness peaks could potentially be utilized to infer the strength of meridional neutral wind.
Currently, rapid prototyping (RP) products are manufactured by layer-based process; this result may cause RP products to break easily along layers when a bending moment is applied. To prevent RP transtibial sockets from breaking, wrapping a layer of unsaturated polyester resin (UPR) around transtibial sockets to reinforce its flexural strength is proposed. To verify the applicability of resin-reinforced RP socket fabrication, two experimental systems, including a socket sensor measurement and gait analysis system, are used to obtain interface pressures between stump, socket and gait characteristics during stance phase while such type of prosthetic socket is used. A male volunteer with a left below-knee amputation, a twenty-year transtibial socket user, was selected for this study. In the experiments, sensors were pasted on the stump and measurement data was collected at different walking speeds. The results of these experiments showed that the interface pressures were concentrated on pressure-tolerant areas, and the swing phase and stride length of stump increased while the volunteer was walking at a fast speed. The resin-reinforced rapid prototyping sockets have better comfortable quality of fitting because the interface pressures are more concentrated on pressure-tolerant areas including the patella tendon and medial tibia flare while wearing the new type of sockets.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.