Biology subjects

Lee, Y.-J.

Publications and source records attributed to Lee, Y.-J..

26 records · Page 2Linked to original sources

bioRxiv2022

Dopamine ameliorates hyperglycemic memory-induced vascular dysfunction in diabetic retinopathy

Dopamine is a neurotransmitter that mediates visual function in the retina, and hyperglycemic memory (HGM) is a pivotal phenomenon in the development of diabetic retinopathy (DR); however, the role of dopamine in HGM-induced retinal vascular dysfunction remains unclear. Here, we report a mechanism of HGM-induced retinal vascular dysfunction and the protective effect of dopamine against the HGM-induced DR. HGM induces retinal vascular lesions through persistent oxidative stress, mitochondrial dysfunction, and microvascular abnormalities after blood glucose normalization, and dopamine ameliorates this HGM-induced retinopathy. HGM induced persistent oxidative stress, mitochondrial membrane potential collapse and fission, and adherens junction disassembly and subsequent vascular leakage in the mouse retinas. These persistent hyperglycemic stresses were inhibited by dopamine treatment in human retinal endothelial cells and by intravitreal injection of levodopa in the retinas of HGM mice. Our findings suggest that dopamine alleviates HGM-induced retinal vascular dysfunction by inhibiting persistent mitochondrial dysfunction and microvascular abnormalities.

biochemistry↗

bioRxiv2021

Metabolic Regulation of Mitochondrial Morphologies in Pancreatic Beta Cells: Bioenergetics-Mitochondrial Dynamics Coupling

Cellular bioenergetics and mitochondrial dynamics are crucial for the secretion of insulin by pancreatic beta cells in response to elevated blood glucose concentrations. To obtain better insights into the interactions between energy production and mitochondrial fission/fusion dynamics, we combine live-cell mitochondria imaging with biophysical-based modeling and network analysis to elucidate the principle regulating mitochondrial morphology to match metabolic demand in pancreatic beta cells. A minimalistic differential equation-based model for beta cells was constructed to include glycolysis, oxidative phosphorylation, simple calcium dynamics, and graph-based fission/fusion dynamics controlled by ATP synthase flux and proton leak flux. The model revealed that mitochondrial fission occurs in response to hyperglycemia, starvation, ATP synthase inhibition, uncoupling, and diabetic condition, in which the rate of proton leak exceeds the rate of mitochondrial ATP synthesis. Under these metabolic challenges, the propensities of tip-to-tip fusion events simulated from the microscopic images of the mitochondrial networks were lower than those in the control group and prevented mitochondrial network formation. The modeling and network analysis could serve as the basis for further detailed research on the mechanisms of bioenergetics and mitochondrial dynamics coupling.

systems biology↗

bioRxiv2021

A Genome-Phenome Association study in native microbiomes identifies a mechanism for cytosine modification in DNA and RNA

Shotgun metagenomic sequencing is a powerful approach to study microbiomes in an unbiased manner and of increasing relevance for identifying novel enzymatic functions. However, the potential of metagenomics to relate from microbiome composition to function has thus far been underutilized. Here, we introduce the Metagenomics Genome-Phenome Association (MetaGPA) study framework, which allows to link genetic information in metagenomes with a dedicated functional phenotype. We applied MetaGPA to identify enzymes associated with cytosine modifications in environmental samples. From the 2365 genes that met our significance criteria, we confirm known pathways for cytosine modifications and proposed novel cytosine-modifying mechanisms. Specifically, we characterized and identified a novel nucleic acid modifying enzyme, 5-hydroxymethylcytosine carbamoyltransferase, that catalyzes the formation of a previously unknown cytosine modification, 5-carbamoyloxymethylcytosine, in DNA and RNA. Our work introduces MetaGPA as a novel and versatile tool for advancing functional metagenomics.

genomics↗

bioRxiv2020

Quantifying myelin content in brain tissue using color spatial light interference microscopy (cSLIM)

Deficient myelination of the brain is associated with neurodevelopmental delays, particularly in high-risk infants, such as those born small in relation to their gestational age (SGA). New methods are needed to further study this condition. Here, we employ Color Spatial Light Interference Microscopy (cSLIM), which uses a brightfield objective and RGB camera to generate pathlength-maps with nanoscale sensitivity in conjunction with a regular brightfield image. Using tissue sections stained with Luxol Fast Blue, the myelin structures were segmented from a brightfield image. Using a binary mask, those portions were quantitatively analyzed in the corresponding phase maps. We first used the CLARITY method to remove tissue lipids and validate the sensitivity of cSLIM to lipid content. We then applied cSLIM to brain histology slices. These specimens are from a previous MRI study, which demonstrated that appropriate for gestational age (AGA) piglets have increased internal capsule myelination (ICM) compared to small for gestational age (SGA) piglets and that a hydrolyzed fat diet improved ICM in both. The identity of samples was blinded until after statistical analyses.

neuroscience↗

bioRxiv2020

Alteration of Power Law Scaling of Spontaneous Brain Activity in Schizophrenia

Nonlinear dynamical analysis has been used to quantify the complexity of brain signal at temporal scales. Power law scaling is a well-validated method in physics that has been used to describe the complex nature of a system across different time scales. In this research, we investigated the change of power-law characteristics in a large-scale resting-state fMRI data of schizophrenia (N = 200) and healthy participants (N = 200) derived from Taiwan Aging and Mental Illness cohort. Fourier transform was used to determine the power spectral density (PSD) of resting-state fMRI signal. We estimated the power law scaling of PSD of resting-state fMRI signal by determining the slope of the regression line fitting to the log-log plot of PSD. The power law scaling represents the dynamical properties of resting-state fMRI signal ranging from noisy oscillation (e.g., white noise) to complex fluctuations (e.g., slope approaches -1). Linear regression model was used to assess the statistical difference in power law scaling between schizophrenia and healthy participants. The significant differences in power law scaling were found in six brain regions. Schizophrenia patients has significantly more positive power law scaling (i.e., frequency components become more homogenous) at four brain regions: left precuneus, left medial dorsal nucleus, right inferior frontal gyrus, and right middle temporal gyrus, compared with healthy participants. Additionally, schizophrenia exhibited less positive power law scaling (i.e., frequency components are more dominant at lower frequency range) in bilateral putamen. Significant correlations of power law scaling with the severity of psychosis were found in these identified brain areas in schizophrenia. These findings suggest that schizophrenia has abnormal brain signal complexity toward random patterns, which is linked to psychotic symptoms. The power law scaling analysis may serve as a novel functional brain imaging marker for evaluating patients with mental illness.

neuroscience↗

bioRxiv2019

Conservation and Divergence of Related Neuronal Lineages in the Drosophila Central Brain

Wiring a complex brain requires enormous cell specificity. This specificity is laid out via a developmental process where neural stem cells produce countless diverse neurons. To help elucidate this process and resolve the considerable dynamic specificity, we need to observe the development of multiple neuronal lineages. Drosophila central brain lineages are predetermined, comprised of a fixed set of neurons born in pairs in a specific order. To reveal specific roles of lineage identity, Notch-dependent sister fate specification, and temporal patterning in morphological diversification, we mapped approximately one quarter of the Drosophila central brain lineages. While we found large aggregate differences, we also discovered similar patterns of morphological specification and diversification. Lineage identity plus Notch state govern primary neuronal trajectories, whereas temporal fates diversify terminal elaborations in target-specific manners. In addition, we identified related lineages of analogous neuron types produced in similar temporal patterns. Two stem cells even yield identical series of dopaminergic neuron types, but with completely disparate sister neurons. These phenomena suggest that large changes in morphological diversity can be the consequence of relatively small differences in lineage fating. Taken together, this large-scale lineage mapping study reveals that relatively simple rules drive incredible neuronal complexity.

developmental biology↗

bioRxiv2019

Long-Term Outcomes of Pediatric Graves Disease Patients Treated with Anti-Thyroid Drugs: Experience from a Taiwan Medical Center

Graves disease (GD) is the most common cause of thyrotoxicosis in children and adolescents, accounting for 15% of all thyroid diseases during childhood. Anti-thyroid drugs (ATD) are recommended as the first-line treatment in children and adolescents. However, the remission rate is lower in children than in adults, and the optimal treatment duration and favorite factors associated with remission remain unknown. We aimed to investigate long-term outcomes of pediatric GD patients receiving ATD. We retrospectively reviewed medical charts of 300 pediatric GD subjects, who were initially treated with ATD and followed up for more than one year, from 1985 to 2017 at MacKay Childrens Hospital. The 300 patients comprised 257 (85.7%) females and 43 (14.3%) males, median age at diagnosis was 11.6 (range 2.7-17.8) years, and median follow-up period was 4.7 (range 1.1-23.9) years. Overall, 122 patients achieved the criteria for discontinuing ATD treatment, seventy-nine (39.9%) patients achieved remission, with a median follow-up period of 5.3 (range 1.5-20.1) years. Patients in the remission group were more likely to be aged < 5 years (remission vs. relapse vs. ongoing ATD; 11.4 vs. 0 vs. 2.6%, P=0.02), less likely to have a family history of thyroid disease (24.1 vs. 42.1 vs. 52.6 %, P=0.001), and had lower TRAb levels (42.8 vs. 53.6 vs. 65.1 %, P=0.02).\n\nConclusionLong-term ATD remains an effective treatment option for GD in children and adolescents. Pediatric GD patients aged < 5 years, having no family history of thyroid disease and having lower TRAb levels were more likely to achieve remission.

physiology↗

bioRxiv2019

Assessing chromatin accessibility in maize using ATAC-seq

Background: Maize is an important crop that has a complex genome. A better understanding of maize chromatin architecture provides great opportunities for crop improvement, because chromatin accessibility influences gene expression, thereby affecting agricultural traits. The newly developed method for chromatin profiling, Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), has been developed to investigate chromatin accessibility. Result: We adapt this method by testing parameters of several key steps and generate the first ATAC-seq protocol for maize. We demonstrate that purification of maize nuclei to eliminate organelles can be achieved without the need for cell sorting, and that only a standard bench-top centrifuge is required for sample preparation. Finally, our sequence analyses confirm that our protocol of ATAC-seq can be successfully used to assess the chromatin landscape in maize. Conclusion: The ATAC-seq provides a useful technique to study the chromatin accessibility. Given the parameters tested in our study, it can be a simple and practical method for maize and may be a foundation for similar studies in other crop species.

genomics↗