Ras proteins are small GTPases localized to the plasma membrane (PM), which regulate cellular proliferation, apoptosis and differentiation. After a series of post-translational modifications, H-Ras and N-Ras traffic to the PM from the Golgi via the classical exocytic pathway, but the exact mechanism of K-Ras trafficking to the PM from the ER is not fully characterized. ATP5G1 (also known as ATP5MC1) is one of the three proteins that comprise subunit c of the F 0 complex of the mitochondrial ATP synthase. In this study, we show that overexpression of the mitochondrial targeting sequence of ATP5G1 perturbs glucose metabolism, inhibits oncogenic K-Ras signaling, and redistributes phosphatidylserine (PtdSer) to mitochondria and other endomembranes, resulting in K-Ras translocation to mitochondria. Also, it depletes phosphatidylinositol 4-phosphate (PI4P) at the Golgi. Glucose supplementation restores PtdSer and K-Ras PM localization and PI4P at the Golgi. We further show that inhibition of the Golgilocalized PI4-kinases (PI4Ks) translocates K-Ras, and PtdSer to mitochondria and endomembranes, respectively. We conclude that PI4P at the Golgi regulates the PM localization of PtdSer and K-Ras. This article has an associated First Person interview with the first author of the paper.
Next generation textile‐based wearable sensing systems will require flexibility and strength to maintain capabilities over a wide range of deformations. However, current material sets used for textile‐based skin contacting electrodes lack these key properties, which hinder applications such as electrophysiological sensing. In this work, a facile spray coating approach to integrate liquid metal nanoparticle systems into textile form factors for conformal, flexible, and robust electrodes is presented. The liquid metal system employs functionalized liquid metal nanoparticles that provide a simple “peel‐off to activate” means of imparting conductivity. The spray coating approach combined with the functionalized liquid metal system enables the creation of long‐term reusable textile‐integrated liquid metal electrodes (TILEs). Although the TILEs are dry electrodes by nature, they show equal skin‐electrode impedances and sensing capabilities with improved wearability compared to commercial wet electrodes. Biocompatibility of TILEs in an in vivo skin environment is demonstrated, while providing improved sensing performance compared to previously reported textile‐based dry electrodes. The “spray on dry—behave like wet” characteristics of TILEs opens opportunities for textile‐based wearable health monitoring, haptics, and augmented/virtual reality applications that require the use of flexible and conformable dry electrodes.
Patients are exposed to iatrogenic injury when hospitalized. In the Tech Care Coordination Program, older veterans with chronic diseases and high healthcare utilization were followed with an in-home technology device, the Health Buddy, and risk management software. Program staff could identify at-risk patients based on their responses to a series of questions about symptoms, behavior, and knowledge. Patients followed in the program for at least 6 months experienced a 45% decrease in hospital admissions, 67% decrease in nursing home admissions, 54% decrease in emergency room visits, and 38% decrease in pharmacy prescriptions. The patients also demonstrated improved compliance with treatment regimens and both patients and providers reported high levels of program satisfaction.
In this study, highly porous, ultrasoft polymeric mats mimicking human tissues were formed from novel polyurethane soft dendritic colloids (PU SDCs). PU SDCs have a unique fibrillar morphology controlled by antisolvent precipitation. When filtered from suspension, PU SDCs form mechanically robust nonwoven mats. The stiffness of the SDC mats can be tuned for physiological relevance. The unique physiochemical characteristics of the PU SDC particles dictate the mechanical properties resulting in tunable elastic moduli ranging from 200 to 800 kPa. The human lung A549 cells cultured on both stiff and soft PU SDC membranes were found to be viable, capable of supporting the air−liquid interface (ALI) cell culture, and maintained barrier integrity. Furthermore, A549 cellular viability and uptake efficiency of aerosolized tannic acid-coated gold nanoparticles (Ta−Au) was found to depend on elastic modulus and culture conditions. Ta−Au nanoparticle uptake was twofold and fourfold greater on soft PU SDCs, when cultured at submerged and ALI conditions, respectively. The significant increase in endocytosed Ta−Au resulted in a 20% decrease in viability, and a 4-fold increase in IL-8 cytokine secretion when cultured on soft PU SDCs at ALI. Common tissue culture materials exhibit super-physiological elastic moduli, a factor found to be critical in analyzing nanomaterial cellular interactions and biological responses.
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