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Jung, Y.

Publications and source records attributed to Jung, Y..

At least 55 records · Page 3Linked to original sources
bioRxiv2021

Cytotoxic Effect of Silver Ions in Combination with Peanut's leaf extract on Cells

As modern people suffered to various infectious diseases such as MERS and Covid 19, people interest in nature-driven health care has increased. Accordingly, expectations for natural therapeutics that can have a beneficial effect on the human body without being processed have increased. Buckwheat, peanut, and pine are representatives. Among them, peanuts contain polyphenols and flavonoids which are used as nutritional foods in various forms. For example, resveratrol is activated by the CYP1B1 enzyme in peanut sprouts and converted to piceatannol that can act on anticancer activity. Accordingly, increasing the content of polyphenols in peanuts makes possible to produce useful substances that are harmless to the human body as well as the environment. Therefore, I conducted research to find an effective way to increase the content of polyphenols. This study projects an effective way to secure peanuts with high polyphenol content based on the characteristics that the content of polyphenols increases when plants are wounded. Comparative studies were conducted through wounding, and it was confirmed that the polyphenol content increased in the wounded plants. Subsequently, it was confirmed that the content of polyphenol increased through the DPPH experiment, and the content of flavonoids also increased. Using the data of this study can be used to produce peanuts with high polyphenol content. To find an effective method for cultivating peanuts containing high concentration of phenolic compounds, I compared two groups of plants with different conditions. First group was consisted of normal plants with no treatment and second group was consisted of wounded plants. I treated by using these conditions in each group for two days and the results showed that group 2 has high concentration of flavonoid and phenolic compounds. To verify this result, I conducted DPPH assay which provides convincing evidence that group 2 has justifiable anti-inflammatory effects. However, due to the difference of the effects in group 1 and 2 was not that standing out, successively added silver ion to observe synergic effect of anti-inflammatory substances. Combined phenolic compound and silver ion showed dramatic effects in nitric oxide (NO) assay for increasing anti-inflammatory effects compared to other examined groups.

pharmacology and toxicology↗
bioRxiv2021

The combined toxicity test of polyester and tetra ethylene glycol on Daphnia magna

The combined toxicity test of polyester and tetra ethylene glycol on Daphnia magna. Globally, wide use of plastics and its increased production has led to a mounting amount of plastic waste entering the natural ecosystems. Due to their small size, plastic particles might be ingested by organisms at the lower end of the food chain and can be transferred by feeding to top consumers. Consequently, plastic pollution in aquatic environments and its potential impact on aquatic life has recently been recognized as an issue of considerable concern for ecosystem. I produced microplastics from 100% polyester thread from Houjix, cut it finely and used a dissecting needle to cut into a size of 5mm or less through a microscope. I also included ethylene glycol to investigate its toxic effects on D. magna. Since my aim was also to compare the toxicity effect of both chemicals, I used different concentrations individually and then in combinations to determine the potential toxic effects of polyester and tetra ethylene glycol (combined and separately) on the life (survival, death) of D. magna. Microplastics from 100% polyester thread from Houjix were produced, into a size of 5mm or less through a microscope. Tetra ethylene glycol was also used to investigate its toxic effects on D. magna. The toxicity effect of both chemicals using different concentrations individually and then in combinations were employed to determine the potential toxic effects of polyester and tetra ethylene glycol (combined and separately) on the life of D. magna. The study exhibited that the IC50 of TEG was higher as compared to polyester which suggests that polyester was more adverse than TEG. Moreover, when TEG and polyester were treated in combination, IC50 value was lower (Figure 3) than the IC50 value of TEG and polyester separately. In other words, the TEG and polyester in combination exhibited the lowest IC50 value in this study. These results suggest that TEG and polyester in combination had adverse effects on the growth and development of D. magna O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/453624v1_fig3.gif" ALT="Figure 3"> View larger version (16K): org.highwire.dtl.DTLVardef@10f7bcorg.highwire.dtl.DTLVardef@1f85fe1org.highwire.dtl.DTLVardef@15ed2b7org.highwire.dtl.DTLVardef@5c161d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOfigure 3.C_FLOATNO polyester and TEG treated on D. magna C_FIG

ecology↗
bioRxiv2021

Therapeutic adenine base editing corrects nonsense mutation and improves visual function in a mouse model of Leber congenital amaurosis

Leber congenital amaurosis (LCA) is an inherited retinal degeneration that causes severe visual dysfunction in children and adolescents. In patients with LCA, pathogenic variants are evident in specific genes, such as RPE65, which are related to the functions of retinal pigment epithelium and photoreceptors. Base editing confers a way to correct pathogenic substitutions without double-stranded breaks in contrast to the original Cas9. In this study, we prepared dual adeno-associated virus vectors containing the split adenine base editors with trans-splicing intein (AAV-ABE) for in vivo adenine base editing in retinal degeneration 12 (rd12) mice, an animal model of LCA, which possess a nonsense mutation of C to T transition in the Rpe65 gene (p.R44X). AAV-ABE induced an A to G transition in retinal pigment epithelial cells of rd12 mice when injected into the subretinal space. The on-target editing was sufficient to recover wild-type mRNA, RPE65 protein, and light-induced electrical responses of retinal tissues. We suggest adenine base editing to correct pathogenic variants in the treatment of LCA.

genetics↗
bioRxiv2020

Task dependence of neural representations of global scene properties but not scene categories in the prefrontal cortex

Natural scenes deliver rich sensory information about the world. Decades of research has shown that the scene-selective network in the visual cortex represents various aspects of scenes. However, less is known about how such complex scene information is processed beyond the visual cortex, such as in the prefrontal cortex. It is also unknown how task context impacts the process of scene perception, modulating which scene content is represented in the brain. In this study, we investigate these questions using scene images from four natural scene categories, which also depict two types of scene attributes, temperature (warm or cold), and sound level (noisy or quiet). A group of healthy human subjects from both sexes participated in the present study using fMRI. In the study, participants viewed scene images under two different task conditions; temperature judgment and sound-level judgment. We analyzed how these scene attributes and categories are represented across the brain under these task conditions. Our findings show that scene attributes (temperature and sound-level) are only represented in the brain when they are task-relevant. However, scene categories are represented in the brain, in both the parahippocampal place area and the prefrontal cortex, regardless of task context. These findings suggest that the prefrontal cortex selectively represents scene content according to task demands, but this task selectivity depends on the types of scene content; task modulates neural representations of scene attributes but not of scene categories. Significance statementResearch has shown that visual scene information is processed in scene-selective regions in the occipital and temporal cortices. Here, we ask how scene content is processed and represented beyond the visual brain, in the prefrontal cortex (PFC). We show that both scene categories and scene attributes are represented in PFC, with interesting differences in task dependency: Scene attributes are only represented in PFC when they are task-relevant, but scene categories are represented in PFC regardless of the task context. Taken together, our work shows that scene information is processed beyond the visual cortex, and scene representation in PFC reflects how adaptively our minds extract relevant information from a scene.

neuroscience↗
bioRxiv2020

Implantable photonic neural probes for light-sheet fluorescence brain imaging

SignificanceLight-sheet fluorescence microscopy is a powerful technique for high-speed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. Here, we demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. AimMass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components. ApproachWe develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200 mm diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed and in vitro mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. ResultsThe probes had 5 to 10 addressable sheets and average sheet thicknesses < 16 m for propagation distances up to 300 m in free space. Imaging areas were as large as {approx} 240 m x 490 m in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. ConclusionsThe neural probes can lead to new variants of light-sheet fluorescence microscopy for deep brain imaging and experiments in freely-moving animals.

bioengineering↗
bioRxiv2020

Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcoholic liver disease

BackgroundIt is unknown whether liver sinusoidal endothelial cells (LSECs) metabolize alcohol. Chronic alcohol consumption decreases endothelial nitric oxide synthase (eNOS)-derived NO production typical of LSEC dysfunction. Heat shock protein 90 (Hsp90) interacts with eNOS to increase its activity. Cytochrome P450 2E1 (CYP2E1) is a key enzyme in alcohol metabolism and facilitates protein acetylation via acetyl-CoA, but its expression in LSECs is unknown. This study investigates alcohol metabolism by LSECs, the mechanism of alcohol-induced LSEC dysfunction and a potential therapeutic approach for alcohol-induced liver injury. MethodsPrimary human, rat and mouse LSECs were used. Histone deacetylase 6 (HDAC6) was overexpressed specifically in liver ECs using an adeno-associated virus (AAV)-mediated gene delivery system to decrease Hsp90 acetylation in ethanol fed mice. ResultsLSECs expressed CYP2E1 and alcohol dehydrogenase 1 (ADH1) and metabolized alcohol. Ethanol induced CYP2E1 in LSECs, but not ADH1. Alcohol metabolism by CYP2E1 increased Hsp90 acetylation and decreased its interaction with eNOS along with a decrease in NO production. A non-acetylation mutant of Hsp90 increased its interaction with eNOS and NO production, whereas a hyper-acetylation mutant decreased NO production, compared with wildtype Hsp90. These results indicate that Hsp90 acetylation is responsible for decreases in its interaction with eNOS and eNOS-derived NO production. Adeno-associated virus 8 (AAV8)-driven HDAC6 overexpression specifically in liver ECs deacetylated Hsp90, restored Hsp90s interaction with eNOS and ameliorated alcohol-induced liver injury in mice. ConclusionRestoring LSEC function is important for ameliorating alcohol-induced liver injury. To this end, blocking acetylation of Hsp90 specifically in LSECs via AAV-mediated gene delivery has the potential to be a new therapeutic strategy.

molecular biology↗
bioRxiv2020

TLR7 ligation augments haematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signalling and enhanced differentiation

Myelodysplastic syndrome (MDS) is a haematological malignancy characterised by blood cytopenias and predisposition to acute myeloid leukaemia (AML). Therapies for MDS are lacking, particularly those that impact the early stages of disease. We developed a model of MDS using zebrafish using knockout of Rps14, the primary mediator of the anaemia associated with del (5q) MDS. These mutant animals display dose- and age-dependent abnormalities in haematopoiesis, culminating in bone marrow failure with dysplastic features. We utilized rps14 knockdown to undertake an in vivo small molecule screen to identify compounds that ameliorate the MDS phenotype, identifying imiquimod, an agonist of TLR7 and TLR8. Imiquimod alleviates anaemia by promoting haematopoietic stem and progenitor cell expansion and erythroid differentiation, the mechanism of which is dependent on TLR7 ligation. TLR7 activation in this setting paradoxically promoted an anti-inflammatory gene signature suggesting crosstalk between pro-inflammatory pathways endogenous to Rps14 loss and TLR7 pathway activation. Finally, we show that in highly purified human bone marrow samples from anaemic patients, imiquimod leads to an increase in erythroid output from myelo-erythroid progenitors and common myeloid progenitors. Our findings have both specific implications for the development of targeted therapeutics for del (5q) MDS and wider significance identifying a potential role for TLR7 ligation in modifying anaemia.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗
bioRxiv2020

A computational study for identifying agronomically important biomarkers using nsSNP data of Korean soybeans

Soybean is a highly nutritious legume grown globally as a food and feed crop. An examination of a collection of 10 cultivated and 6 wild Korean soybean varieties showed that there is phenotypic variability notable in different soybeans. Therefore, to develop a list of biomarker candidates useful for growing soybeans of better quality and quantity, The genes of 16 Korean soybean varieties were compared with those of the reference Glycine max var. Williams 82. The comparison was made through gene sequencing to facilitate selection of nsSNPs. The objective of the study was to find out the structural and functional variations caused by nsSNPs and discuss whether the collection of Korean soybean varieties qualifies as biomarkers based on their phenotypic traits. Analysis of the data collected was done using four software: SIFT, Polyphen, PANTHER, and I-mutant 2.0, which are designed to detect the rate of functional and structural variations caused by the nsSNPs in cultivated and wild soybean varieties. Genotypic information obtained in the analysis was used to develop a core collection of biomarkers based on whether nsSNP content was found in more than half of the 16 samples. Therefore, the list of biomarker candidates developed from this study showed that Korean soybean could provide valuable information needed in both future crop genetic research and identification of biomarkers.

genomics↗
bioRxiv2020

CD45 pre-exclusion from the tips of microvilli establishes a phosphatase-free zone for early TCR triggering

The tyrosine phosphatase CD45 is a major gatekeeper for restraining T cell activation. Its exclusion from the immunological synapse (IS) is crucial for TCR signal transduction. Here, we used expansion super-resolution microscopy to reveal that CD45 is pre-excluded from the tips of microvilli on primary T cells prior to antigen encounter. This pre-exclusion was diminished by depleting cholesterol or by engineering the transmembrane domain of CD45 to increase its membrane integration length, but was independent of the CD45 extracellular domain. We further show that brief microvilli-mediated contacts can induce Ca2+ influx in mouse antigen-specific T cells engaged by antigen-pulsed APCs. We propose that the absence of CD45 phosphatase activity at the tips of microvilli enables or facilitates TCR triggering from brief T cell-APC contacts before formation of a stable IS, and that these microvilli-mediated contacts represent the earliest step in the initiation of a T cell adaptive immune response. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/109074v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@24d116org.highwire.dtl.DTLVardef@11b029borg.highwire.dtl.DTLVardef@4817e9org.highwire.dtl.DTLVardef@119ec32_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗
bioRxiv2020

Single-cell transcriptomics reveals zone-specific alterations of liver sinusoidal endothelial cells in cirrhosis

Dysfunction of liver endothelial cells (ECs), particularly sinusoidal endothelial cells (LSECs), is permissive for the progression of liver fibrosis/cirrhosis and responsible for its clinical complications. Here, we have mapped the spatial distribution of heterogeneous liver ECs in normal versus cirrhotic mouse livers and identified zone-specific transcriptomic changes of LSECs associated with liver cirrhosis using single-cell RNA sequencing technology. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs and 1 cluster of lymphatic ECs. To add finer detail, we mapped the 3 clusters of LSECs to Zones 1 to 3. We found that heterogeneous liver EC identities are conserved even in liver cirrhosis and that Zone 3 LSECs are most susceptible to damage associated with liver cirrhosis, demonstrating increased capillarization and decreased ability to regulate endocytosis. Altogether, this study deepens our knowledge of the pathogenesis of liver cirrhosis at a spatial, cell-specific level, which is indispensable for the development of novel therapeutic strategies to target the most highly dysfunctional liver ECs.

cell biology↗
bioRxiv2020

Although host-related factors are important for the formation of gut microbiota, environmental factors cannot be ignored

The gut microbiome is essential to human health. However, little is known about the influence of the environment versus host-related factors (e.g. genetic background, sex, age, and body mass) in the formation of human intestinal microflora. Here, we present evidence in support of the importance of host-related factors in the establishment and maintenance of individual gut assemblages. We collected fecal samples (n = 249) from 44 Korean naval trainees and 39 healthy people living in Korea over eight weeks and sequenced the bacterial 16S rRNA genes. The following hypotheses were tested: 1) microbiome function is linked to its diversity, community structure, and genetic host-related factors, and 2) preexisting host-related factors have a more significant effect on gut microbiome formation and composition than environmental factors. For each individual, the difference between the initial gut microbiota and that after eight weeks was negligible even though the 44 naval trainees lived in the same area and received the same diet, the same amount of exercise, and the same amount of physical stress during the study. This suggests that host-related factors, rather than environmental factors, is a key determinant of individual gut microflora. Moreover, eight weeks of physical training and experiencing the same environmental conditions resulted in an increase in the species Bifidobacterium, Faecalibacterium, and Roseburia in most trainees, suggesting a healthier intestinal environment. IMPORTANCEIn order to understand the role of human gut microbiome, it is important to know how individuals gut microbiota are formed. In this study, we tested the host-related factors versus environmental factors to affect gut microbiome and found that the former have a more association. However, we also found that the controlled environment give an effect on the gut microflora as well. This study provides preliminary evidence that differences in the formation and diversity of gut microbiota within a population could be determined by host-related factors rather than environmental factors.

microbiology↗
bioRxiv2019

Transfer Learning for Predicting Conversion from Mild Cognitive Impairment to Dementia of Alzheimer Type based on 3D-Convolutional Neural Network

Dementia of Alzheimers Type (DAT) is associated with a devastating and irreversible cognitive decline. As a pharmacological intervention has not yet been developed to reverse disease progression, preventive medicine will play a crucial role for patient care and treatment planning. However, predicting which patients will progress to DAT is difficult as patients with Mild Cognitive Impairment (MCI) could either convert to DAT (MCI-C) or not (MCI-NC). In this paper, we develop a deep learning model to address the heterogeneous nature of DAT development. Structural magnetic resonance imaging was utilized as a single biomarker, and a three-dimensional convolutional neural network (3D-CNN) was developed. The 3D-CNN was trained using transfer learning from the classification of Normal Control and DAT scans at the source task. This was applied to the target task of classifying MCI-C and MCI-NC scans. The model results in 82.4% classification accuracy, which outperforms current models in the field. Furthermore, by implementing an occlusion map approach, we visualize key brain regions that significantly contribute to the prediction of MCI-C and MCI-NC. Results show the hippocampus, amygdala, cerebellum, and pons regions as significant to prediction, which are consistent with current understanding of disease. Finally, the models prediction value is significantly correlated with rates of change in clinical assessment scores, indicating the model is able to predict an individual patients future cognitive decline. This information, in conjunction with the identified anatomical features, will aid in building a personalized therapeutic strategy for individuals with MCI. This model could also be useful for selection of participants for clinical trials.

bioinformatics↗
bioRxiv2019

Reduction of insulin/IGF-1 receptor rejuvenates immunity via positive feedback circuit

Immunosenescence is considered an inevitable decline in immune function during aging. Here we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically delays immunosenescence and rejuvenates immunity in C. elegans. We find that p38 mitogen-activated protein kinase 1 (PMK-1), a key determinant of immunosenescence, is dispensable for this rejuvenated immunity. Instead, we demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase immunocompetence in old daf-2(-) animals. The upregulation of DAF-16/FOXO and HSF-1 decreases the expression of the zip-10/bZIP transcription factor, which in turn downregulates INS-7, an agonistic insulin-like peptide, resulting in further reduction of insulin/IGF-1 signaling (IIS). Thus, reduced IIS bypasses immunosenescence and rejuvenates immunity via the upregulation of anti-aging transcription factors that modulate an endocrine insulin-like peptide through a positive feedback mechanism. Because many functions of IIS are conserved across phyla, our study may lead to the development of strategies for human immune rejuvenation.

genetics↗
bioRxiv2019

iScore: an MPI supported software for ranking protein-protein docking models based on a random walk graph kernel and support vector machines.

Computational docking is a promising tool to model three-dimensional (3D) structures of protein-protein complexes, which provides fundamental insights of protein functions in the cellular life. Singling out near-native models from the huge pool of generated docking models (referred to as the scoring problem) remains as a major challenge in computational docking. We recently published iScore, a novel graph kernel based scoring function. iScore ranks docking models based on their interface graph similarities to the training interface graph set. iScore uses a support vector machine approach with random-walk graph kernels to classify and rank protein-protein interfaces.\n\nHere, we present the software for iScore. The software provides executable scripts that fully automatize the computational workflow. In addition, the creation and analysis of the interface graph can be distributed across different processes using Message Passing interface (MPI) and can be offloaded to GPUs thanks to dedicated CUDA kernels.

bioinformatics↗
bioRxiv2019

NEURONS THAT FUNCTION WITHIN AN INTEGRATOR TO PROMOTE A PERSISTENT BEHAVIORAL STATE IN DROSOPHILA

Innate behaviors involve both reflexive motor programs and internal states. In Drosophila, optogenetic activation of male-specific P1 interneurons triggers courtship song, as well as a persistent behavioral state that prolongs courtship and enhances aggressiveness. Here we identify pCd neurons as persistently activated by repeated P1 stimulation. pCd neurons are required for P1-evoked persistent courtship and aggression, as well as for normal social behavior. Activation of pCd neurons alone is inefficacious, but enhances and prolongs courtship or aggression promoted by female cues. Transient female exposure induced persistent increases in male aggressiveness, an effect suppressed by transiently silencing pCd neurons. Transient silencing of pCd also disrupted P1-induced persistent physiological activity, implying a requisite role in persistence. Finally, P1 activation of pCd neurons enhanced their responsiveness to cVA, an aggression-promoting pheromone. Thus, pCd neurons function within a circuit that integrates P1 input, to promote a persistent internal state that enhances multiple social behaviors.

neuroscience↗
bioRxiv2019

The conserved metalloprotease invadolysin is present in invertebrate haemolymph and vertebrate blood

We identified invadolysin, a novel essential metalloprotease, for functions in chromosome structure, cell proliferation and migration. Invadolysin also plays an important metabolic role in insulin signaling and is the only protease known to localise to lipid droplets, the main lipid storage organelle in the cell. In silico examination of the protein sequence of invadolysin predicts not only protease and lipase catalytic motifs, but also post-translational modifications and the secretion of invadolysin. Here we show that the protease motif of invadolysin is important for its role in lipid accumulation, but not in glycogen accumulation. The lipase motif does not appear to be functionally important for accumulation of lipids or glycogen. Post-translational modifications likely contribute to modulating the level, localisation or activity of invadolysin. We identified a secreted form of invadolysin in the soluble fraction of invertebrate hemolymph (where we observe sexually dimorphic forms) and also vertebrate plasma, including in the extracellular vesicle fraction. Biochemical analysis for various post-translational modifications demonstrated that secreted invadolysin is both N-and O-glycosylated, but not apparently GPI-linked. The discovery of invadolysin in the extracellular milieu suggests a role for invadolysin in normal organismal physiology.\n\nSummary StatementIn this study, we show that the conserved metalloprotease invadolysin is present in invertebrate hemolymph and vertebrate blood, suggesting the protein may function in organismal physiology.

cell biology↗
bioRxiv2018

iScore: A novel graph kernel-based function for scoring protein-protein docking models

Protein complexes play a central role in many aspects of biological function. Knowledge of the three-dimensional (3D) structures of protein complexes is critical for gaining insights into the structural basis of interactions and their roles in the biomolecular pathways that orchestrate key cellular processes. Because of the expense and effort associated with experimental determination of 3D structures of protein complexes, computational docking has evolved as a valuable tool to predict the 3D structures of biomolecular complexes. Despite recent progress, reliably distinguishing near-native docking conformations from a large number of candidate conformations, the so-called scoring problem, remains a major challenge. Here we present iScore, a novel approach to scoring docked conformations that combines HADDOCK energy terms with a score obtained using a graph representation of the protein-protein interfaces and a measure of evolutionary conservation. It achieves a scoring performance competitive with, or superior to that of the state-of-the-art scoring functions on independent data sets consisting docking software-specific data sets and the CAPRI score set built from a wide variety of docking approaches. iScore ranks among the top scoring approaches on the CAPRI score set (13 targets) when compared with the 37 scoring groups in CAPRI. The results demonstrate the utility of combining evolutionary and topological, and physicochemical information for scoring docked conformations. This work represents the first successful demonstration of graph kernel to protein interfaces for effective discrimination of near-native and non-native conformations of protein complexes. It paves the way for the further development of computational methods for predicting the structure of protein complexes.

bioinformatics↗