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Biology subjects

Murai, S.

Publications and source records attributed to Murai, S..

4 recordsLinked to original sources

Hmgb1 release kinetics shape its extracellular functions during regulated cell death

Danger-associated molecular patterns (DAMPs), such as high mobility group protein B1 (HMGB1), are released from dying cells, yet the kinetics and functional consequences of their release remain unclear. Using Hmgb1-mCherry transgenic mice and live-cell imaging, we visualize Hmgb1 and interleukin-1{beta} (IL-1{beta}) secretion at single-cell resolution. Hmgb1 exhibits two distinct release kinetics: short-duration completed within 1 min and long duration spanning several minutes. Mathematical modeling demonstrates that short-duration release generates substantially higher local Hmgb1 concentrations and steeper gradients near the dying cell than long-duration release. Such rapid release may enable one or a few dying cells to produce sufficient Hmgb1 to stimulate neighboring cells, consistent with its role as an alarmin. In vivo imaging of cisplatin-induced kidney injury reveals an inverse correlation between intracellular Hmgb1 levels and monocyte infiltration. Together, these findings suggest that Hmgb1 release kinetics shape its extracellular functions during regulated cell death.

cell biology↗

A FRET biosensor, SMART, monitors necroptosis in renal tubular epithelial cells in a cisplatin-induced kidney injury model

Necroptosis is a regulated form of cell death involved in various pathological conditions, including ischemic reperfusion injuries, virus infections, and drug-induced tissue injuries. However, it is not fully understood when and where necroptosis occurs in vivo. We previously generated a Forster resonance energy transfer (FRET) biosensor, termed SMART (the sensor for MLKL activation based on FRET), which specifically monitored necroptosis in human and murine cell lines in vitro. Here, we generated transgenic (Tg) mice that expressed the SMART biosensor in various tissues. SMART monitored necroptosis, but not apoptosis or pyroptosis, in primary cells, including peritoneal macrophages and embryonic fibroblasts. Moreover, the FRET signal was elevated in renal tubular cells of cisplatin-treated SMART Tg mice compared to untreated SMART Tg mice. Together, SMART Tg mice may provide a valuable tool for monitoring necroptosis in different types of cells in vitro and in vivo.

cell biology↗

Reward priming differentially modulates enhancement and inhibition in auditory decision-making

In cognitive sciences, rewards, such as money and food, play a fundamental role in individuals daily lives and well-being. Moreover, rewards that are irrelevant to the task alter individuals behavior. However, it is unclear whether explicit knowledge of reward irrelevancy has an impact on reward priming enhancements and inhibition. In this study, an auditory change-detection task with task-irrelevant rewards was introduced. The participants were informed explicitly in advance that the rewards would be given randomly. The results revealed that while inhibition related to reward priming only occurred when the participants were explicitly informed about rewards, implicit instruction thereof resulted in enhancement and inhibition associated with reward priming. These findings highlight the contribution of explicit information about rewards associated with auditory decisions.

neuroscience↗

Temporal dynamics of endogenous attentional modulation without cue awareness

Invisible visual stimuli can regulate our broad cognitive performance in the pursuit of current goals. Endogenous spatial attention is an important modulator of cognitive performance, and it can be triggered by unconscious cues. However, how its effect changes with time remains unclear. Here, we show that endogenous attention was triggered by an arrow-cue whose direction participants reported being unaware of but which affected the task performance in a time-dependent manner. Participants were asked to remember the directions of eight Landolt c rings (target memory array) after arrow-cue presentation, which was designed to orient their attention to a certain c ring. Then, we applied a delay, ranging from 83 ms to 1000 ms, between the arrow-cue and the target memory array presentation (the possible delays were equally spaced on a logarithmic scale). The attentional effect was greater for the 83, 183, 250 and 333 ms delays than the other six possible delays. In contrast, its effect was maintained irrespective of the delay when the participants reported being aware of the cue direction. Thus, awareness of arrow-cue direction was necessary to maintain endogenous attentional modulation, and its modulation without arrow-cue direction awareness was limited in a time-dependent manner.

neuroscience↗