Biology subjects

Oyama, S.

Publications and source records attributed to Oyama, S..

4 recordsLinked to original sources

bioRxiv2026

High extracellular osmolarity promotes yeast thermotolerance through osmotic modulation and glycerol-dependent adaptation.

High-temperature stress is a major constraint on yeast growth and fermentation, and has traditionally been interpreted primarily in terms of intracellular molecular damage such as protein denaturation and aggregation. Despite this extensive focus on intracellular mechanisms, how physical factors within the extracellular environment influence yeast thermotolerance remains poorly understood. Here we demonstrate that increases in extracellular osmolarity markedly attenuate growth inhibition under high-temperature conditions in yeast. This protective effect was consistently observed in multiple laboratory and industrial strains of Saccharomyces cerevisiae, as well as in ascomycetous and basidiomycetous yeasts, indicating that osmotic pressure-dependent thermotolerance is a broadly conserved phenomenon. We also found that extracellular osmolarity dynamically increases during growth and then decreases in a diauxic shift-like pattern after growth arrest. At high temperature, the secretion of glucose-derived metabolites decreased, but that of other solutes increased, suggesting that heat stress alters the composition of extracellular solutes contributing to osmolarity. In addition, intracellular glycerol levels increased at high temperature, and this increase was further enhanced under high-osmolarity conditions. Notably, expression of a constitutively active Hog1 mutant exhibited raised intracellular glycerol levels, enhanced nuclear localization of Hog1, and improved growth under high-temperature conditions. Collectively, these findings support a model in which extracellular osmolarity is modulated to avoid excessive intracellular osmolarity under high-temperature conditions, while the intracellular accumulation of glycerol contributes to yeast adaptation at high-temperature. Our results highlight extracellular-intracellular osmotic coordination as an additional physiological layer of high-temperature stress adaptation in yeast.

microbiology↗

bioRxiv2024

Filtered Point Processes Tractably Capture Rhythmic And Broadband Power Spectral Structure in Neural Electrophysiological Recordings

AO_SCPLOWBSTRACTC_SCPLOWNeural electrophysiological recordings arise from interacting rhythmic (oscillatory) and broadband (aperiodic) biological subprocesses. Both rhythmic and broadband processes contribute to the neural power spectrum, which decomposes the variance of a neural recording across frequencies. Although an extensive body of literature has successfully studied rhythms in various diseases and brain states, researchers only recently have systematically studied the characteristics of broadband effects in the power spectrum. Broadband effects can generally be categorized as 1) shifts in power across all frequencies, which correlate with changes in local firing rates and 2) changes in the overall shape of the power spectrum, such as the spectral slope or power law exponent. Shape changes are evident in various conditions and brain states, influenced by factors such as excitation to inhibition balance, age, and various diseases. It is increasingly recognized that broadband and rhythmic effects can interact on a sub-second timescale. For example, broadband power is time-locked to the phase of <1 Hz rhythms in propofol induced unconsciousness. Modeling tools that explicitly deal with both rhythmic and broadband contributors to the power spectrum and that capture their interactions are essential to help improve the interpretability of power spectral effects. Here, we introduce a tractable stochastic forward modeling framework designed to capture both narrowband and broadband spectral effects when prior knowledge or theory about the primary biophysical processes involved is available. Population-level neural recordings are modeled as the sum of filtered point processes (FPPs), each representing the contribution of a different biophysical process such as action potentials or postsynaptic potentials of different types. Our approach builds on prior neuroscience FPP work by allowing multiple interacting processes and time-varying firing rates and by deriving theoretical power spectra and cross-spectra. We demonstrate several properties of the models, including that they divide the power spectrum into frequency ranges dominated by rhythmic and broadband effects, and that they can capture spectral effects across multiple timescales, including sub-second cross-frequency coupling. The framework can be used to interpret empirically observed power spectra and cross-frequency coupling effects in biophysical terms, which bridges the gap between theoretical models and experimental results.

neuroscience↗

bioRxiv2023

UBL3 Interacts with Alpha-synuclein in Cells and the Interaction is Downregulated by the EGFR Pathway Inhibitor Osimertinib

Ubiquitin-like 3 (UBL3) acts as a post-translational modification (PTM) factor and regulates protein sorting into small extracellular vesicles (sEVs). sEVs have been reported as vectors for the pathology propagation of neurodegenerative diseases, such as -synucleinopathies. Alpha-synuclein (-syn) has been widely studied for its involvement in -synucleinopathies. However, it is still unknown whether UBL3 interacts with -syn, and is influenced by drugs or compounds. In this study, we investigated the interaction between UBL3 and -syn, and any ensuing possible functional and pathological implications. We found that UBL3 can interact with -syn by the Gaussia princeps based split luciferase complementation assay in cells and immunoprecipitation, while cysteine residues at its C-terminal, which are considered important as PTM factors for UBL3, were not essential for the interaction. The interaction was upregulated by 1-methyl-4-phenylpyridinium exposure. In drug screen results, the interaction was significantly downregulated by the treatment of osimertinib. These results suggest that UBL3 interacts with -syn in cells and be significantly downregulated by epidermal growth factor receptor (EGFR) pathway inhibitor osimertinib. Therefore, the UBL3 pathway may be a new therapeutic target for -synucleinopathies in the future.

molecular biology↗

bioRxiv2019

Natural brown adipose expansion and remission of hyperglycemia in obese SM/J mice

Disruption of glucose homeostasis increases the risk of type II diabetes, cardiovascular disease, stroke, and cancer. We leverage a novel rodent model, the SM/J mouse, to understand glycemic control in obesity. On a high fat diet, obese SM/J mice initially develop impaired glucose tolerance and elevated fasting glucose. Strikingly, their glycemic dysfunction resolves by 30 weeks of age despite persistence of obesity. A prominent phenotype is that they dramatically expand their brown adipose depots as they resolve glycemic dysfunction. This occurs naturally and spontaneously on a high fat diet, with no temperature or genetic manipulation. When the brown adipose depot is removed from normoglycemic obese mice, fasting blood glucose and glucose tolerance revert to unhealthy levels, and animals become insulin resistant. We identified 267 genes whose expression changes in the brown adipose when the mice resolve their unhealthy glycemic parameters, and find the expanded tissue has a healthier expression profile of cytokines and extracellular matrix genes. We describe morphological, physiological, and transcriptomic changes that occur during the unique brown adipose expansion and remission of glycemic dysfunction in obese SM/J mice. Understanding this phenomenon in mice will open the door for innovative therapies aimed at improving glycemic control in obesity. Significance StatementSome obese individuals maintain normal glycemic control. Despite being obese, these individuals have low risk for metabolic complications, including type-II diabetes. If we better understood why some obese people maintain normoglycemia then we might develop new approaches for treating metabolic complications associated with obesity. However, the causative factors underlying glycemic control in obesity remain unknown. We discovered that, despite persistence of the obese state, SM/J mice enter into diabetic remission: returning to normoglycemia and reestablishing glucose tolerance and improving insulin sensitivity. A prominent phenotype is that they dramatically expand their brown adipose depots as they resolve glycemic dysfunction. Understanding this phenomenon in mice will open the door for innovative therapies aimed at improving glycemic control in obesity.

physiology↗