Biology subjects

Ryu, S.

Publications and source records attributed to Ryu, S..

6 recordsLinked to original sources

bioRxiv2018

Real-time non-invasive intracranial state estimation using unscented Kalman filter

Intracranial pressure (ICP) monitoring is desirable as a first-line measure to assist decision-making in cases of increased ICP. Clinically, non-invasive ICP monitoring is also required to avoid infection and hemorrhage in patients. The relationships among the arterial blood pressure (Pa), ICP, cerebral blood flow, and its velocity (QCBFv) measured by transcranial Doppler ultrasound measurement have been reported. However, real-time non-invasive ICP estimation using these modalities is less well documented. Here, we present a novel algorithm for real-time and non-invasive ICP monitoring with QCBFv and Pa, called direct-current (DC)-ICP. This technique is compared with invasive ICP for 11 traumatic-brain-injury patients admitted to Cheju Halla Hospital and Gangnam Severance Hospital from July 2017 to June 2018. The inter-subject correlation coefficient between true and estimate was 0.70. The AUCs of the ROCs for prediction of increased ICP for the DC-ICP methods are 0.816. Thus, QCBFv monitoring can facilitate reliable real-time ICP tracking with our novel DC-ICP algorithm, which can provide valuable information under clinical conditions.

neuroscience↗

bioRxiv2018

40 Hz acoustic stimulation decreases amyloid beta and modulates brain rhythms in a mouse model of Alzheimers disease

IntroductionThe accumulation of amyloid-beta (A{beta}) is one of the neuropathologic hallmarks of Alzheimers disease (AD) and abnormal gamma band oscillations and brain connectivity have been observed. Recently, a therapeutic potential of gamma entrainment of the brain was reported by Iaccarino et al. However, the affected areas were limited to hippocampus and visual cortex. Therefore, we sought to test the effects of acoustic stimulation in a mouse model of AD.\n\nMethodsFreely moving 6-month-old 5XFAD mice with electroencephalogram (EEG) electrodes were treated with daily two-hour acoustic stimulation at 40Hz for 2 weeks. A{beta} and microglia were evaluated by immunohistochemistry and ELISA. Evoked and spontaneous gamma power were analyzed by wavelet analysis. Coherence, phase locking value (PLV), and cross-frequency coupling were analyzed.\n\nResultsThe number of A{beta} plaques decreased in the pre-and infralimbic (PIL) and hippocampus regions and soluble A{beta}-40 and A{beta}-42 peptides in PIL in the acoustic stimulation group. We also found that the number of microglia increased in PIL and hippocampus. In EEG analysis, evoked gamma power was decreased and spontaneous gamma power was increased. Gamma coherence and phase locking value did not show significant changes. Cross-frequency coupling was shifted from gamma-delta to gamma-theta rhythm.\n\nConclusionIn summary, we found that acoustic stimulation at 40Hz can reduce A{beta} in the brain and restore the gamma band oscillations and the frontoparietal connectivity. Our data suggest that acoustic stimulation might alter the natural deterioration processes of AD and have a therapeutic potential in AD.

neuroscience↗

bioRxiv2018

Exceptional Solvent Tolerance in Yarrowia lipolytica Is Enhanced by Sterols

Microbial biocatalysis in organic solvents such as ionic liquids (ILs) is attractive for making fuels and chemicals from complex substrates including lignocellulosic biomass. However, low IL concentrations of 0.5-1.0 % (v/v) can drastically inhibit microbial activity. In this study, we engineered an exceptionally robust oleaginous yeast Yarrowia lipolytica, YlCW001, by adaptive laboratory evolution (ALE). The mutant YlWC001 shows robust growth in up to 18% (v/v) 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), which makes it the most IL-tolerant microorganism published to our knowledge. Remarkably, YlCW001 exhibits broad tolerance in most commonly used hydrophilic ILs beyond [EMIM][OAc]. Scanning electron microscopy revealed that ILs significantly damage cell wall and/or membrane of wildtype Y. lipolytica with observed cavities, dents, and wrinkles while YlCW001 maintains healthy morphology even in high concentrations of ILs up to 18% (v/v). By performing comprehensive metabolomics, lipidomics, and transcriptomics to elucidate this unique phenotype, we discovered that both wildtype Y. lipolytica and YlCW001 reconfigured membrane composition (e.g., glycerophospholipids and sterols) and cell wall structure (e.g., chitin) under IL-stressful environments. By probing the steroid pathway at transcriptomic, enzymatic, and metabolic levels, we validated that sterols (i.e., ergosterol) are a key component of the cell membrane that enables Y. lipolytica to resist IL-responsive membrane damage and hence tolerate high IL concentrations. This study provides a better understanding of exceptional robustness of Y. lipolytica that can be potentially harnessed as a microbial manufacturing platform for production of fuels and chemicals in organic solvents.

microbiology↗

bioRxiv2017

Accurate estimation of neural population dynamics without spike sorting

A central goal of systems neuroscience is to relate an organisms neural activity to behavior. Neural population analysis often begins by reducing the dimensionality of the data to focus on the patterns most relevant to a given task. A major practical hurdle to data analysis is spike sorting, and this problem is growing rapidly as the number of neurons measured increases. Here, we investigate whether spike sorting is necessary to estimate neural dynamics. The theory of random projections suggests that we can accurately estimate the geometry of low-dimensional manifolds from a small number of linear projections of the data. We re-analyzed data from three previous studies and found that neural dynamics and scientific conclusions are quite similar using multi-unit threshold crossings in place of sorted neurons. This finding unlocks existing data for new analyses and informs the design and use of new electrode arrays for laboratory and clinical use.

neuroscience↗

bioRxiv2017

A theory of multineuronal dimensionality, dynamics and measurement

In many experiments, neuroscientists tightly control behavior, record many trials, and obtain trial-averaged firing rates from hundreds of neurons in circuits containing billions of behaviorally relevant neurons. Di-mensionality reduction methods reveal a striking simplicity underlying such multi-neuronal data: they can be reduced to a low-dimensional space, and the resulting neural trajectories in this space yield a remarkably insightful dynamical portrait of circuit computation. This simplicity raises profound and timely conceptual questions. What are its origins and its implications for the complexity of neural dynamics? How would the situation change if we recorded more neurons? When, if at all, can we trust dynamical portraits obtained from measuring an infinitesimal fraction of task relevant neurons? We present a theory that answers these questions, and test it using physiological recordings from reaching monkeys. This theory reveals conceptual insights into how task complexity governs both neural dimensionality and accurate recovery of dynamic portraits, thereby providing quantitative guidelines for future large-scale experimental design.

neuroscience↗

bioRxiv2017

Understanding Functional Roles of Native Pentose-Specific Transporters for Activating Dormant Pentose Metabolism in Yarrowia lipolytica

Pentoses including xylose and arabinose are the second-most prevalent sugars of lignocellulosic biomass that can be harnessed for biological conversion. Although Yarrowia lipolytica has emerged as a promising industrial microorganism for production of high-value chemicals and biofuels, its native pentose metabolism is poorly understood. Our previous study demonstrated that Y. lipolytica (ATCC MYA-2613) has endogenous enzymes for D-xylose assimilation, but inefficient xylitol dehydrogenase causes Y. lipolytica to assimilate xylose poorly. In this study, we investigated the functional roles of native sugar-specific transporters for activating the dormant pentose metabolism in Y. lipolytica. By screening a comprehensive set of 16 putative pentose-specific transporters, we identified two candidates, YALI0C04730p and YALI0B00396p, that enhanced xylose assimilation. The engineered mutants YlSR207 and YlSR223, overexpressing YALI0C04730p and YALI0B00396p, respectively, improved xylose assimilation approximately 23% and 50% in comparison to YlSR102, a parent engineered strain overexpressing solely the native xylitol dehydrogenase gene. Further, we activated and elucidated a widely unknown, native L-arabinose-assimilating pathway in Y. lipolytica through transcriptomic and metabolic analyses. We discovered that Y. lipolytica can co-consume xylose and arabinose, where arabinose utilization shares transporters and metabolic enzymes of some intermediate steps of the xylose-assimilating pathway. Arabinose assimilation was synergistically enhanced in the presence of xylose while xylose assimilation was competitively inhibited by arabinose. L-arabitol dehydrogenase is the rate-limiting step responsible for poor arabinose utilization in Y. lipolytica. Overall, this study sheds light on the cryptic pentose metabolism of Y. lipolytica and further helps guide strain engineering of Y. lipolytica for enhanced assimilation of pentose sugars.\n\nIMPORTANCEThe oleaginous yeast Yarrowia lipolytica is a promising industrial platform microorganism for production of high-value chemicals and fuels. For decades since its isolation, Y. lipolytica has often been known to be incapable of assimilating pentose sugars, xylose and arabinose, that are dominantly present in lignocellulosic biomass. Through bioinformatic, transcriptomic and enzymatic studies, we have uncovered the dormant pentose metabolism of Y. lipolytica. Remarkably, unlike most yeast strains that share the same transporters for importing hexose and pentose sugars, we discovered that Y. lipolytica possess the native pentose-specific transporters. By overexpressing these transporters together with the rate-limiting D-xylitol and L-arabitol dehydrogenases, we activated the dormant pentose metabolism of Y. lipolytica. Overall, this study provides a fundamental understanding of the dormant pentose metabolism of Y. lipolytica and guides future metabolic engineering of Y. lipolytica for enhanced conversion of pentose sugars to high-value chemicals and fuels.

physiology↗