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Purpose: Nuclear accumulation of YAP/TAZ promotes tumorigenesis in several cancers, including melanoma. Although the mechanisms underlying the nuclear retention of YAP are known, those underlying the retention of TAZ remain unclear. Our study investigates a novel acetylation/deacetylation switch in TAZ, governing its subcellular localization in melanoma tumorigenesis. Methods: Immunoprecipitation/Western blot assessed TAZ protein interactions and acetylation. SIRT5 activity was quantified with enzyme-linked immunosorbent assay. Immunofluorescence indicated TAZ nuclear localization. TEAD transcriptional activity was measured through luciferase reporter assays. ChIP detected TAZ binding to the CTGF promoter. Transwell and wound healing assays quantified melanoma cell invasiveness and migration. Metastasis was evaluated using a mouse model via tail vein injections. Clinical relevance was explored via immunohistochemical staining of patient tumors. Results: CBP facilitated TAZ acetylation at K54 in response to epidermal growth factor stimulation, while SIRT5 mediated deacetylation. Acetylation correlated with phosphorylation, regulating TAZ's binding with LATS2 or TEAD. TAZ K54 acetylation enhanced its S89 phosphorylation, promoting cytosolic retention via LATS2 interaction. SIRT5-mediated deacetylation enhanced TAZ-TEAD interaction and nuclear retention. Chromatin IP showed SIRT5-deacetylated TAZ recruited to CTGF promoter, boosting transcriptional activity. In a mouse model, SIRT5 overexpression induced melanoma metastasis to lung tissue following the injection of B16F10 melanocytes via the tail vein, and this effect was prevented by verteporfin treatment. Conclusions: Our study revealed a novel mechanism of TAZ nuclear retention regulated by SIRT5-mediated K54 deacetylation and demonstrated the significance of TAZ deacetylation in CTGF expression. This study highlights the potential implications of the SIRT5/TAZ axis for treating metastatic melanoma. [ABSTRACT FROM AUTHOR]

This study aims to improve the efficiency of task switching in hospital laboratories. In a laboratory, several medical technicians perform multiple tasks. Technicians are not aware of the marginal amount of time it takes to switch between tasks, and this accumulation of lost minutes can cause the technician to worry more about the remaining working time than work quality. They rush through their remaining tasks, thereby rendering their work less efficient. For time optimization, we identified work changeover times to help maintain the work quality in the laboratory while reducing the number of task switching instances. We used the turnaround time (TAT) compliance rate of emergency room samples as an indicator to evaluate laboratory performance and the number of task switching instances as an index of the task performer perspective (TPP). We experimented with a monitoring system that populates the time for sample classification according to the optimal time for task switching. Through the proposed methodology, we successfully reduced not only the instances of task switching by 10% but also the TAT non-compliance rate from 4.97 to 2.66%. Consequently, the introduction of new methodology has greatly increased work efficiency. [ABSTRACT FROM AUTHOR]

The coefficient of lateral stress at rest, $$\hbox {K}_{0}$$ , is an important soil parameter that characterizes the geostatic stress state of soils. In this study, an experimental testing program was established to investigate the values of $$\hbox {K}_{0}$$ for granular materials that are subject to freezing and thawing. Various material conditions, including different fines contents, relative densities and freezing-thawing cycles, were considered in the testing program. The values of $$\hbox {K}_{0}$$ for thawed condition were higher than for unfrozen condition with net volume decrease. The effect of freezing and thawing became more pronounced as fines content increased while the effect of relative density was small. From the multi-cycled freezing-thawing tests, it was observed that the increase in $$\hbox {K}_{0}$$ was most significant during the first freezing-thawing cycle. For frozen condition, the values of $$\hbox {K}_{0}$$ were very low up to a certain limit stress level. Beyond the limit stress level, the values of $$\hbox {K}_{0}$$ became higher and close to those of unfrozen condition. The increases in $$\hbox {K}_{0}$$ with net volume decrease after freezing and thawing process was explained with internal changes in microstructure and stress state of soils. [ABSTRACT FROM AUTHOR]