Biology subjects

Jung, J.-H.

Publications and source records attributed to Jung, J.-H..

9 recordsLinked to original sources

bioRxiv2026

Systematic histone mutagenesis reveals nucleosome-dependent maintenance of three-dimensional chromosome architecture and virulence in Cryptococcus neoformans

BackgroundGenomic stability is maintained through the coordinated regulation of DNA repair, dNTP pool balance, and histone dynamics--the three pillars of the DNA damage response. Because histones constitute the fundamental 3D physical scaffold of the genome, their precise regulation is essential for the spatial organization that dictates environmental fitness. In the radiotolerant pathogen Cryptococcus neoformans, the Rad53-Bdr1 pathway is a central DDR mediator; however, the mechanisms linking this checkpoint to histone dynamics remain poorly understood. Because conventional one-dimensional analyses cannot capture how spatial chromatin folding shapes transcriptional reprogramming, we integrated high-throughput chromosome conformation capture (Hi-C) with transcriptomic profiling to address this gap. ResultsWe demonstrate that HTA1 and HTB1, encoding H2A and H2B, are essential for viability, whereas H3 and H4 paralogs exhibit functional redundancy. Although most core histones are regulated by Rad53, HHT1 and variant HTZ1 are expressed independently of the Rad53. Notably, loss of the H3 paralog HHT2 induces growth defects under diverse stress conditions. Integrated RNA sequencing and Hi-C analyses reveal that HHT2 deletion drives transcriptional reprogramming of stress-responsive genes, coinciding with large-scale chromatin rearrangements such as A/B compartment switching and topologically associating domain boundary shifts. Furthermore, HHT2 loss impairs virulence factor formation and attenuates virulence. ConclusionOur findings identify core histones as essential architects of the 3D genome in C. neoformans. By establishing a causal link between chromatin structural collapse and transcriptional reprogramming, this study highlights 3D genome architecture as a decisive physical switch linking nucleosome-level dynamics to global transcriptional programs required for environmental survival.

microbiology↗

bioRxiv2025

A nuclear pore complex component HOS1 mediates UV-B light-induced UVR8 nuclear localization for activating HY5 cascade in Arabidopsis

Upon ultraviolet-B (UV-B) exposure, the photoreceptor UVR8 translocates to the nucleus and interacts with COP1 to activate downstream transcription factors, notably including HY5. However, the mechanism of UVR8 nuclear import has remained unclear1,2. Here, we identified HOS1, a component of the nuclear pore complex (NPC), as a key mediator of UVR8 nuclear translocation under UV-B conditions. HOS1 directly interacts with UVR8 specifically in response to UV-B, facilitating its efficient import into the nucleus. Consistent with this role, HOS1-deficient mutants exhibit reduced HY5 protein accumulation, compromised UV-B tolerance, and impaired expression of HY5- regulated genes, including those involved in anthocyanin synthesis. These findings reveal a novel role of HOS1 in bridging UV-B perception in the cytoplasm and gene transcriptional activation in the nucleus by enabling UVR8 nuclear import. They highlight a distinct broader role of NPC components in coordinating plant transcriptional response to environmental stimuli.

plant biology↗

bioRxiv2024

Human stem cell-derived GABAergic interneuron development reveals early emergence of subtype diversity followed by gradual electrochemical maturation

Medial ganglionic eminence-derived inhibitory GABAergic pallial interneurons (MGE-pINs) are essential regulators of cortical circuits; their dysfunction is associated with numerous neurological disorders. We developed human (h) MGE-pINs from pluripotent stem cells for the treatment of drug-resistant epilepsy. Here, we analyzed xenografted hMGE-pINs over the lifespan of host mice using single nuclei RNA sequencing. Comparative transcriptomics against endogenous human brain datasets revealed that 97% of grafted cells developed into somatostatin (SST) and parvalbumin (PVALB) subtypes, including populations that exhibit selective vulnerability in Alzheimers disease. Transplanted hMGE-pINs demonstrated rapid emergence of subclass features, progressing through distinct transcriptional states sequentially involving neuronal migration, synapse organization, and membrane maturation. We present molecular, electrophysiological, and morphological data that collectively confirm the derivation of diverse bona-fide human SST and PVALB subtypes, providing a high-fidelity model to study human MGE-pIN development and functional maturation as well as a compositional atlas for regenerative cell therapy applications.

neuroscience↗

bioRxiv2024

Efficacy of foramen magnum decompression with and without cranioplasty in a rat model of Chiari-like malformation

In veterinary medicine, canine Chiari-like malformation (CLM) disease is surgically managed through foramen magnum decompression (FMD) with cranioplasty. This study aimed to assess the efficacy of cranioplasty surgery by establishing a rat CLM model and then applying FMD with and without cranioplasty and comparing the outcomes. Twenty-four 8-week-old male Sprague-Dawley rats underwent surgery to induce CLM by reducing the caudal cranial fossa volume, mimicking cerebellum herniation. The rats were randomly and equally assigned to three groups: a control group (induced CLM), an FO group (induced CLM rats undergoing FMD only), and a CR group (induced CLM rats undergoing FMD with cranioplasty). At 11 weeks of age, the FO and CR groups underwent FMD surgery. Four weeks later, magnetic resonance imaging (MRI) was used to measure the cisterna magna volume to assess surgical outcomes. Post-surgery MRI revealed that the mean cisterna magna volume was 23.82 {+/-} 1.70, 34.88 {+/-} 4.39, and 29.48 {+/-} 2.20 mm3 in the control, FO, and CR groups, respectively. There was a significant increase in the cisterna magna volume in the FO and CR groups compared to that in the control group (p < 0.05), with the FO group showing a significantly greater increase than the CR group (p < 0.05). These findings suggest that FMD surgery alone is more effective at restoring the cisterna magna volume than FMD surgery with cranioplasty. FMD surgery alone resulted in a greater increase in cisterna magna volume than FMD with cranioplasty in our rat CLM model, suggesting that FMD alone may be more effective to treat canine CLM. These findings challenge the typical approach of combining FMD with cranioplasty in treating canine CLM disease and underscore the need for further investigation into optimizing surgical techniques for CLM.

zoology↗

bioRxiv2024

Glyoxalase 1: emerging biomarker and therapeutic target in cervical cancer progression

IntroductionCervical cancer presents a significant global health challenge, disproportionately impacting underserved populations with limited access to healthcare. Early detection and effective management are vital in addressing this public health concern. This study focuses on Glyoxalase-1 (GLO1), an enzyme crucial for methylglyoxal detoxification, in the context of cervical cancer. MethodsWe assessed GLO1 expression in cervical cancer patient samples using immunohistochemistry. In vitro experiments using HeLa cell lines were conducted to evaluate the impact of GLO1 inhibition on cell viability and migration. Single-cell RNA sequencing (scRNA-seq) and gene set variation analysis were utilized to investigate GLO1s role in the metabolism of cervical cancer. Additionally, public microarray data were analyzed to determine GLO1 expression across various stages of cervical cancer. ResultsOur analysis included 58 cervical cancer patients, and showed that GLO1 is significantly upregulated in cervical cancer tissues compared to normal cervical tissues, independent of pathological findings and disease stage. In vitro experiments indicated that GLO1 downregulation decreased cell viability and migration in cervical cancer cell lines. Analyses of scRNA-seq data and public gene expression datasets corroborated the overexpression of GLO1 and its involvement in cancer metabolism, particularly glycolysis. An examination of expression data from precancerous lesions revealed a progressive increase in GLO1 expression from normal tissue to invasive cervical cancer. ConclusionsThis study highlights the critical role of GLO1 in the progression of cervical cancer, presenting it as a potential biomarker and therapeutic target. These findings contribute valuable insights towards personalized treatment approaches and augment the ongoing efforts to combat cervical cancer. Further research is necessary to comprehensively explore GLO1s potential in clinical applications. SynopsisThis study examines Glyoxalase-1 (GLO1) in cervical cancer and reveals its significant upregulation in cancerous tissues compared to normal counterparts. In vitro experiments show that downregulating GLO1 decreases cell viability and migration. Single-cell RNA sequencing and gene expression analysis substantiate GLO1s involvement in cancer metabolism, notably in glycolysis. These findings identify GLO1 as a potential biomarker and therapeutic target, offering insights for personalized treatment approaches in cervical cancer management.

cancer biology↗

bioRxiv2021

Preprocessing of general stenotic vascular flow data for topological data analysis

A new analysis and classification method of vascular disease based on topological data analysis (TDA) has been proposed in [1]. The proposed method utilizes the application of persistent homology to hemodynamic variables. Particularly, 2D homology is obtained from the velocity field of the flow projected onto the unit sphere, known as so-called the S2 projection. It was shown that such homology is closely related to the degree of vascular disease. The original method was developed based on the computational fluid dynamic (CFD) solutions of the straight stenotic vessels. In this paper, we develop a preprocessing method that enables the proposed TDA method to be applied to general stenotic vessels of irregular geometry. The velocity field is subject to a coordinate transformation correcting for orientation and curved geometry. The preprocessed data is projected onto S2 and the corresponding homology is calculated. We show that this preprocessing is necessary for the proposed TDA method to be successfully applied to general types of stenotic vessels. Validation was performed on a set of clinical data including reconstructed vascular geometry with corresponding diagnostic indices.

biophysics↗

bioRxiv2020

Role of PIF4 and FLC in controlling flowering time under daily variable temperature profile

Initiation of flowering is a crucial developmental event that requires both internal and environmental signals to determine when floral transition should occur to maximize reproductive success. Ambient temperature is one of the key environmental signals that highly influence flowering time, not only seasonally but also in the context of drastic temperature fluctuation due to global warming. Molecular mechanisms of how high or low constant temperatures affect the flowering time have been largely characterized in the model plant Arabidopsis thaliana; however, the effect of natural daily variable temperature outside laboratories is only partly explored. Several groups of flowering genes have been shown to play important roles in temperature responses, including two temperature-responsive transcription factors (TFs), namely PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and FLOWERING LOCUS C (FLC), that act antagonistically to regulate flowering time by activating or repressing floral integrator FLOWERING LOCUS T (FT). In this study, we have demonstrated that the daily variable temperature (VAR) causes early flowering in both natural accessions Col-0, C24 and their late flowering hybrid C24xCol, which carries both functional floral repressor FLC and its activator FRIGIDA (FRI), as compared to a constant temperature (CON). The loss-of-function mutation of PIF4 exhibits later flowering in VAR, suggesting that PIF4 at least in part, contributes to acceleration of flowering in response to the daily variable temperature. We find that VAR increases PIF4 transcription at the end of the day when temperature peaks at 32 {degrees}C. The FT transcription is also elevated in VAR, as compared to CON, in agreement with earlier flowering observed in VAR. In addition, VAR causes a decrease in FLC transcription in 4-week-old plants, and we further show that overexpression of PIF4 can reduce FLC transcription, suggesting that PIF4 might also regulate FT indirectly through the repression of FLC. To further conceptualize an overall model of gene regulatory mechanisms involving PIF4 and FLC in controlling flowering in response to temperature changes, we construct a co-expression - transcriptional regulatory network by combining publicly available transcriptomic data and gene regulatory interactions of our flowering genes of interest and their partners. The network model reveals the conserved and tissue-specific regulatory functions of 62 flowering-time-relating genes, namely PIF4, PIF5, FLC, ELF3 and their immediate neighboring genes, which can be useful for confirming and predicting the functions and regulatory interactions between the key flowering genes.

plant biology↗

bioRxiv2019

Topological data analysis of vascular disease: A theoreticalframework

Vascular disease is a leading cause of death world wide and therefore the treatment thereof is critical. Understanding and classifying the types and levels of stenosis can lead to more accurate and better treatment of vascular disease. Some clinical techniques to measure stenosis from real patient data are invasive or of low accuracy.\n\nIn this paper, we propose a new methodology, which can serve as a supplementary way of diagnosis to existing methods, to measure the degree of vascular disease using topological data analysis. We first proposed the critical failure value, which is an application of the 1-dimensional homology group to stenotic vessels as a generalization of the percent stenosis. We demonstrated that one can take important geometric data including size information from the persistent homology of a topological space. We conjecture that we may use persistent homology as a general tool to measure stenosis levels for many different types of stenotic vessels.\n\nWe also proposed the spherical projection method, which is meant to allow for future classification of different types and levels of stenosis. We showed empirically using the spectral approximation of different vasculatures that this projection could provide a new medical index that measures the degree of vascular disease. Such a new index is obtained by calculating the persistence of the 2-dimensional homology of flows. We showed that the spherical projection method can differentiate between different cases of flows and reveal hidden patterns about the underlying blood flow characteristics, that is not apparent in the raw data. We showed that persistent homology can be used in conjunction with this technique to classify levels of stenosis.\n\nThe main interest of this paper is to focus on the theoretical development of the framework for the proposed method using a simple set of vascular data.

physiology↗

bioRxiv2018

Two-dimensional local Fourier image reconstruction via domain decomposition Fourier continuation method

The MRI image is obtained in the spatial domain from the given Fourier coefficients in the frequency domain. It is costly to obtain the high resolution image because it requires higher frequency Fourier data while the lower frequency Fourier data is less costly and effective if the image is smooth. However, the Gibbs ringing, if existent, prevails with the lower frequency Fourier data. We propose an efficient and accurate local reconstruction method with the lower frequency Fourier data that yields sharp image profile near the local edge. The proposed method utilizes only the small number of image data in the local area. Thus the method is efficient. Furthermore the method is accurate because it minimizes the global effects on the reconstruction near the weak edges shown in many other global methods for which all the image data is used for the reconstruction. To utilize the Fourier method locally based on the local non-periodic data, the proposed method is based on the Fourier continuation method. This work is an extension of our previous 1D Fourier domain decomposition method to 2D Fourier data. The proposed method first divides the MRI image in the spatial domain into many subdomains and applies the Fourier continuation method for the smooth periodic extension of the subdomain of interest. Then the proposed method reconstructs the local image based on L2 minimization regularized by the L1 norm of edge sparsity to sharpen the image near edges. Our numerical results suggest that the proposed method should be utilized in dimension-by-dimension manner instead of in a global manner for both the quality of the reconstruction and computational efficiency. The numerical results show that the proposed method is effective when the local reconstruction is sought and that the solution is free of Gibbs oscillations.

neuroscience↗