Myosin phosphatase targeting subunit1 controls localization and motility of Rab7-containing vesicles: Is myosin phosphatase a cytoplasmic dynein regulator?

Myosin phosphatase targeting subunit1 (MYPT1) is a critical subunit of myosin phosphatase (MP), which brings PP1Cδ phosphatase and its substrate together. We previously showed that MYPT1 depletion resulted in oblique chromatid segregation. Therefore, we hypothesized that MYPT1 may control microtubule-dependent motor activity. Dynein, a minus-end microtubule motor, is known to be involved in mitotic spindle assembly. We thus examined whether MYPT1 and dynein may interact. Proximity ligation assay and co-immunoprecipitation revealed that MYPT1 and dynein intermediate chain (DIC) were associated. We found that DIC phosphorylation is increased in MYPT1-depleted cells in vivo, and that MP was able to dephosphorylate DIC in vitro. MYPT1 depletion also altered the localization and motility of Rab7-containing vesicles. MYPT1-depletion dispersed the perinuclear Rab7 localization to the peripheral in interphase cells. The dispersed Rab7 localization was rescued by microinjection of a constitutively active, truncated MYPT1 mutant, supporting that MP is responsible for the altered Rab7 localization. Analyses of Rab7 vesicle trafficking also revealed that minus-end transport was reduced in MYPT1-depleted cells. These results suggest an unexpected role of MP: MP controls dynein activity in both mitotic and interphase cells, possibly by dephosphorylating dynein subunits including DIC.

Study of Alarm Threshold for Assumed Nasogastric Tube Self-removal Action Using a Contact Sensor System.

Physical restraints negatively impact the physical, mental, and social well-being of patients. However, elderly people with dementia are often physically restrained by preventing nasogastric tube (NG tube) self-removal. This study aimed to examine alarm threshold settings limited to the actions that the subject makes contact with the NG tube out of feeling uneasy for the NG tube (assumed self-removal actions) using a contact sensor system in order to achieve non-physical restraint. In this study, subjects with experience in caring for older people with dementia were required to perform an assumed self-removal action along with 15 kinds of non-self-removal actions, while we observed the contact detection and measured the voltage. The alarm thresholds for the assumed self-removal action were examined from the ROC curve using the voltage zero time and the number of times the voltage was up and down during each action as a variable. The system presented in this study allowed us to reduce the false alarm rate from 23.3% to 8.5%. Furthermore, we used this alarm threshold to verify the data of three new subjects, observing a false alarm rate of 0.0%. Our future research would focus on investigating and evaluating elderly with dementia using the alarm threshold of the assumed self-removal action that we examined. In addition, we would use ICT to link contact detection with the nurse call system. Clinical Relevance- In this study, we examined the alarm threshold limited to the expected self-removal action using a contact sensor system. We showed that it is possible to detect the NG tube self-removal with few false alarms.

Examination of a contact detection sensor to prevent self-removal of peripheral intravenous catheters.

If patients are at risk of self-removal of a catheter, it is necessary to check the condition of the catheter frequently. If this is the only way to prevent self-removal, physical restraint of the patient is required. Furthermore, it is currently necessary to reduce human-to-human contact to prevent COVID-19 infection. Therefore, the development of a sensor system to prevent self-removal of a catheter and reduce human-to-human contact is urgent. The purpose of this study is to examine a sensor system that detects the contact of a patient's hand to a peripheral intravenous catheter in order to prevent self-removal in patients with dementia. This study analyzes the use of a capacitance sensor and an energization sensor to detect the contact of a patient's hand to a catheter. Additionally, the time required from the start of peeling the sensor sheet to the removal of the needle was measured. As the results, the capacitance sensor was difficult to use in a clinical setting because the connection between the seat and cable could be unstable depending on the condition of the connections. The energization sensor was able to recognize the contact of a hand to the catheter by detecting its contact with the sensor. It took at least 28 seconds from detection of the hand contact to the beginning of needle removal. Therefore, it is possible for the caregiver to visit the patient's bedside and stop the self-removal when the sensor sheet detects hand contact. This study is the first step in developing the system that prevents self-removal by detecting hand contact and requires several more steps for clinical use. In the future, we will conduct surveys on more subjects and clinical trials on elderly with dementia to examine accuracy, precision, and repeatability. Using the energization sensor, a self-removal prevention system for dementia patients will be further developed.Clinical Relevance- Developing this self-removal prevention system in the future will allow many dementia patients to no longer be physically restrained, and it will make it possible to remotely detect their actions to prevent self-removal while also minimizing the risk of COVID-19 infection.

Investigation of Fascin1, a Marker of Mature Dendritic Cells, Reveals a New Role for IL-6 Signaling in CCR7-Mediated Chemotaxis.

Migration of mature dendritic cells (DCs) to lymph nodes is critical for the initiation of adaptive immunity. CCR7, a G-protein-coupled receptor for CCL19/21 chemokines, is known to be essential for chemotaxis of mature DCs, but the molecular mechanism linking inflammation to chemotaxis remains unclear. We previously demonstrated that fascin1, an actin-bundling protein, increases chemotaxis of mature mouse DCs. In this article, we demonstrated that fascin1 enhanced IL-6 secretion and signaling of mature mouse DCs. Furthermore, we demonstrated that IL-6 signaling is required for chemotaxis. Blockage of IL-6 signaling in wild-type DCs with an anti-IL-6 receptor α (IL-6Rα) Ab inhibited chemotaxis toward CCL19. Likewise, knockout of IL-6Rα inhibited chemotaxis of bone marrow-derived DCs. The addition of soluble IL-6Rα and IL-6 rescued chemotaxis of IL-6Rα knockout bone marrow-derived DCs, underscoring the role of IL-6 signaling in chemotaxis. We found that IL-6 signaling is required for internalization of CCR7, the initial step of CCR7 recycling. CCR7 recycling is essential for CCR7-mediated chemotaxis, explaining why IL-6 signaling is required for chemotaxis of mature DCs. Our results have identified IL-6 signaling as a new regulatory pathway for CCR7/CCL19-mediated chemotaxis and suggest that rapid migration of mature DCs to lymph nodes depends on inflammation-associated IL-6 signaling.