Biology subjects

Miyazaki, M.

Publications and source records attributed to Miyazaki, M..

23 records · Page 2Linked to original sources

bioRxiv2021

T cell-intrinsic vitamin A metabolism and its signaling are targets for memory T cell-based cancer immunotherapy

Memory T cells play an essential role in infectious and tumor immunity. Vitamin A metabolites such as retinoic acid are immune modulators, but the role of vitamin A metabolism in memory T- cell differentiation is unclear. In this study, we identified retinol dehydrogenase 10 (Rdh10), which metabolizes vitamin A to retinal (RAL), as a key molecule for regulating T cell differentiation. T cell-specific Rdh10 deficiency enhanced memory T-cell formation through blocking RAL production in infection model. Epigenetic profiling revealed that retinoic acid receptor (RAR) signaling activated by vitamin A metabolites induced comprehensive epigenetic repression of memory T cell-associated genes, including TCF7, thereby promoting effector T-cell differentiation. Importantly, memory T cells generated by Rdh10 deficiency and blocking RAR signaling elicited potent anti-tumor responses in adoptive T-cell transfer setting. Thus, T cell differentiation is regulated by vitamin A metabolism and its signaling, which should be novel targets for memory T cell-based cancer immunotherapy.

immunology↗

bioRxiv2021

Age-dependent formation of TMEM106B amyloid filaments in human brain

Many age-dependent neurodegenerative diseases, like Alzheimers and Parkinsons, are characterised by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-{beta} (A{beta}), -synuclein and TDP-43 are the most common. Here, we used electron cryo-microscopy (cryo-EM) structure determination to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in the human brain. We solved cryo-EM structures of TMEM106B filaments from the brains of 22 individuals with neurodegenerative conditions, including sporadic and inherited tauopathies, A{beta}-amyloidoses, synucleinopathies and TDP-43opathies, as well as from the brains of two neurologically normal individuals. We observed three different TMEM106B folds, with no clear relationship between folds and diseases. The presence of TMEM106B filaments correlated with that of a 29 kDa sarkosyl-insoluble fragment of the protein on Western blots. The presence of TMEM106B filaments in the brains of older, but not younger, neurologically normal individuals indicates that they form in an age-dependent manner.

neuroscience↗

bioRxiv2021

"XR Mark Test" Reveals Sensorimotor Body Representation in Toddlers

Research on multisensory integration--particularly visuo-proprioceptive integration--has renewed interest in how body representation develops in early childhood. In the past decade, researchers have attempted to adapt body-illusion tasks such as the rubber hand illusion for young children, yet difficulties with verbal reports and inconsistent behavioral responses limit their usefulness for toddlers. At the same time, children naturally begin to recognize their mirror image as self during the early toddler period, suggesting that mirror-based localization may offer a developmentally appropriate window onto emerging body representation. However, the classic mark test is not suitable for repeated measurements. We developed Bodytoypo, a cross-reality body-part localization task that projects a life-size self-image onto a screen and overlays AR markers on multiple body locations using real-time skeleton detection. Toddlers touched the corresponding location on their actual body, allowing quantitative evaluation of localization accuracy. Thirty 2- and 3-year-olds participated. We recorded first-touch outcomes, touch error, reaction times, and hand trajectories. Conventional coding was combined with an automated statistical analysis to estimate factors predicting touch error. Results showed that Bodytoypo is feasible for repeated use with toddlers and provides reliable indices of body-part localization. Automated statistical analyses identified several reaching strategies that appeared to reflect differences in localization precision. These findings suggest age-related changes in how visual information and motor prediction are weighted during visuo-proprioceptive integration. Bodytoypo offers a promising behavioral index for clarifying how sensorimotor information (body schema) and spatial understanding of body parts (body topology) jointly contribute to the early development of body representation.

animal behavior and cognition↗

bioRxiv2021

A Novel Mouse Wound Model for Scar Tissue Formation in Abdominal-Muscle Wall

Scar tissue formation is a result of excess healing reactions after wounding. Hypertrophic scars scarcely develop in a mouse. In the present study, we established a novel experimental model of a scar-forming wound by resecting a small portion of the abdominal wall on the lower center of the abdomen, which exposed contractive forces by the surrounding muscle tissue. As a tension-less control, a back-skin excision model was used with a splint fixed onto the excised skin edge, and granulation tissue formed on the muscle facia supported by the back skeleton. One week after the resection, initial healing reactions such as fibroblast proliferation took place in both models. However, after 21 days, lesions with collagen-rich granulation tissues forming multiple nodular/spherical-like structures developed only in the abdominal-wall model. The lesions are analogous to scar lesions in humans. Such lesions, however, did not develop in the back-skin excision model. Therefore, this animal model is unique in that fibrous scar tissues form under a physiological condition without using any artificial factors and is valuable for studying the pathogenesis and preclinical treatment of scar lesions. Summary StatementScar lesions are hardly developed in animals. We thus developed a scar lesion in mice without using any artificial factors. The model is reliable, reproducible, and valuable.

pathology↗

bioRxiv2019

Isolation of an archaeon at the prokaryote-eukaryote interface

The origin of eukaryotes remains enigmatic. Current data suggests that eukaryotes may have risen from an archaeal lineage known as \"Asgard archaea\". Despite the eukaryote-like genomic features found in these archaea, the evolutionary transition from archaea to eukaryotes remains unclear due to the lack of cultured representatives and corresponding physiological insight. Here we report the decade-long isolation of a Lokiarchaeota-related Asgard archaeon from deep marine sediment. The archaeon, \"Candidatus Prometheoarchaeum syntrophicum strain MK-D1\", is an anaerobic, extremely slow-growing, small cocci ([~]550 nm), that degrades amino acids through syntrophy. Although eukaryote-like intracellular complexities have been proposed for Asgard archaea, the isolate has no visible organella-like structure. Ca. P. syntrophicum instead displays morphological complexity - unique long, and often, branching protrusions. Based on cultivation and genomics, we propose an \"Entangle-Engulf-Enslave (E3) model\" for eukaryogenesis through archaea-alphaproteobacteria symbiosis mediated by the physical complexities and metabolic dependency of the hosting archaeon.

microbiology↗