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Sugiyama, T.

Publications and source records attributed to Sugiyama, T..

3 recordsLinked to original sources

Reinforcement meta-learning optimizes visuomotor learning

Reinforcement learning enables the brain to learn optimal action selection, such as go or not go, by forming state-action and action-outcome associations. Does this mechanism also optimize the brains willingness to learn, such as learn or not learn? Learning to learn by rewards, i.e., reinforcement meta-learning, is a crucial mechanism for machines to develop flexibility in learning, which is also considered in the brain without empirical examinations. Here, we show that humans learn to learn or not learn to maximize rewards in visuomotor learning tasks. We also show that this regulation of learning is not a motivational bias but is a result of an instrumental, active process, which takes into account the learning-outcome structure. Our results thus demonstrate the existence of reinforcement meta-learning in the human brain. Because motor learning is a process of minimizing sensory errors, our findings uncover an essential mechanism of interaction between reward and error.

neuroscience

The Ccr4-Not complex monitors the translating ribosome for codon optimality

Control of mRNA decay rate is intimately connected to translation elongation but the spatial coordination of these events is poorly understood. The Ccr4-Not complex initiates mRNA decay through deadenylation and activation of decapping. Using a combination of cryo-electron microscopy, ribosome profiling and mRNA stability assays we show recruitment of Ccr4-Not to the ribosome via specific interaction of the Not5 subunit with the ribosomal E-site. This interaction only occurs when the ribosome lacks accommodated A-site tRNA, indicative of low codon optimality. Loss of Not5 results in the inability of the mRNA degradation machinery to sense codon optimality. Our analysis elucidates a physical link between the Ccr4-Not complex and the ribosome providing mechanistic insight into the coupling of decoding efficiency with mRNA stability.

molecular biology

Angiocrine factors from HUVECs amplify erythroid cells

Erythropoiesis is regulated by microenvironmental factors from the vasculature. Enhanced erythropoiesis, which occurs under stress or during development, amplifies erythroid cells to meet the demand of red blood cells. This process uncouples cell division and differentiation, thus the accumulated erythroid cells remain undifferentiated in the vasculature. However, little is known about how vascular endothelial cells (ECs) regulate erythropoiesis. Here we identified that human umbilical vein endothelial cells (HUVECs) keep erythroid cells undifferentiated and amplify their number. We determined that HUVECs amplify erythroid cells via secreted angiocrine factors. The expression profile of these factors suggested that they resemble macrophage-crines for enhanced erythropoiesis. Molecularly, HUVECs mediate the activation of ERK signaling. These data indicate that angiocrine factors from HUVECs enhance erythropoiesis via the amplification of undifferentiated erythroid cells. Our study contributes to the ultimate goal of harnessing erythropoiesis to replace blood transfusions.

developmental biology