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Jung, B.

Publications and source records attributed to Jung, B..

18 recordsLinked to original sources
bioRxiv2026

Charting neuroimaging-based head circumference and cranial shape across development

Quantitative assessment of head growth supports early detection of neurological disease, yet current clinical practice relies on manual measurements that are variable, anatomically limited, and difficult to scale. Here we introduce a fully automated imaging-native framework (CranioTrace) that transforms routine neuroimaging into standardized, population-referenced markers of cranial development. By integrating topology-constrained segmentation, contour regularization, and geometry-based quality control for automated slice selection, CranioTrace robustly extracts head circumference and cranial morphology from heterogeneous MRI and CT data without manual intervention. The framework enabled construction of sex-specific population growth models across pediatric development in a dataset comprising 9,685 scans spanning birth to early adulthood across 25 cohorts. Imaging-derived head circumference shows strong agreement with tape measurements across independent datasets, high reproducibility (intraclass correlation up to 0.99), and consistent performance across modalities. Beyond conventional head circumference, CranioTrace quantifies cranial shape and asymmetry, capturing developmental dynamics that are not accessible through conventional measurements. Population modeling reveals rapid early-life expansion followed by nonlinear deceleration and stable sex differences. Application to neurogenetic cohorts identifies disease-consistent shifts in growth trajectories: head circumference was higher in neurofibromatosis type 1 and 16p11.2 deletion and lower in 22q11.2 deletion and 16p11.2 duplication. By converting clinical imaging archives into scalable cranial phenotypes linked to probabilistic reference models, CranioTrace provides a foundation for imaging-based growth charting, integrated skull-brain phenotyping, and precise assessment of neurodevelopment.

neuroscience↗
bioRxiv2024

Brain Charts for the Rhesus Macaque Lifespan

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

neuroscience↗
bioRxiv2023

Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates ageing in mice

Nucleolar stress (NS) has been associated to several age-related diseases such as cancer or neurodegeneration. To investigate the mechanisms of toxicity triggered by NS, we here used (PR)n arginine-rich peptides that are found in patients of some neurodegenerative diseases. Although these peptides accumulate at nucleoli and generate NS, how this translates into cellular toxicity is poorly understood. We here reveal that whereas (PR)n expression leads to an overall decrease in protein abundance, this occurs concomitant with an accumulation of free ribosomal (r) proteins in the cytoplasm, a hallmark of ribosomopathies. Conversely, cells with acquired resistance to (PR)n peptides present global downregulation of r-proteins and low levels of mTOR signaling. In mice, systemic expression of (PR)97 drives widespread NS and accelerated ageing, which is associated to an increased expression of r-proteins and mTOR hyperactivation. Furthermore, the reduced lifespan of (PR)97-expressing mice was alleviated by the mTOR inhibitor rapamycin. Importantly, we show that the generalised accumulation of free r-proteins is a common outcome in response to chemical or genetic perturbations that trigger NS, such as Actinomycin D, TIF-IA depletion, or the expression of mutant HMGB1 variants recently associated to rare human diseases. Together, our study presents in vivo evidence supporting the role of NS as a driver of ageing, and provides a general framework to explain the toxicity caused by NS in mammalian cells.

molecular biology↗
bioRxiv2022

Therapeutic activation of endothelial sphingosine 1-phosphate receptor-1 by chaperone-bound S1P suppresses proliferative retinal vasculopathy

Sphingosine-1-phosphate (S1P), a bioactive lipid mediator that signals via G protein-coupled S1P receptors (S1PR), is required for normal vascular development. The role of this signaling axis in vascular retinopathies is largely unexplored. Here we show in a mouse model of oxygen-induced retinopathy (OIR) that endothelial overexpression of S1pr1 suppresses while endothelial knockout (KO) of S1pr1 worsens neovascular tuft formation. Furthermore, neovascular tufts are increased in Apom KO mice which lack HDL-bound S1P while they are suppressed in Apom TG mice which has more circulating HDL-S1P. These results suggest that circulating HDL-S1P activation of endothelial S1PR1 specifically suppresses proliferative retinal vasculopathy. Moreover, systemic administration of ApoM-Fc-bound S1P or a small molecule Gi-biased S1PR1 agonist suppressed neovascular tuft formation. Circulating HDL-S1P activation of endothelial S1PR1 may be a key protective mechanism to guard against neovascular retinopathies that occur not only in premature infants but also in diabetes and aging.

pathology↗
bioRxiv2022

High-resolution epigenetic profiling identifies novel regulators of COPD in human lung fibroblasts

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering the environmental cause of COPD (e.g., cigarette smoke) and disease phenotypes, including stem-cell senescence and impaired differentiation, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease. The epigenetic landscape is markedly changed in lung fibroblasts across COPD stages, with DNA methylation changes occurring predominantly in regulatory regions, including promoters and enhancers. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Notably, we identified epigenetic and transcriptional dysregulation already in mild COPD patients, providing unique insights into early disease. Integration of profiling data identified 110 candidate regulators of disease phenotypes, including epigenetic factors. Using phenotypic screens, we verified the regulator capacity of multiple candidates and linked them to repair processes in the human lung. Our study provides first integrative high-resolution epigenetic and transcriptomic maps of human lung fibroblasts across stages of COPD. We reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression and identify new candidate regulators involved in the pathogenesis of chronic respiratory diseases. The presence of various epigenetic factors among the candidates demonstrates that epigenetic regulation in COPD is an exciting research field that holds promise for novel therapeutic avenues for patients.

cell biology↗
bioRxiv2022

Endothelial-derived sphingolipids are required for vascular development and systemic lipid homeostasis

Serine palmitoyl transferase (SPT), the rate-limiting enzyme in the de novo synthesis of sphingolipids (SL), is needed for embryonic development, physiological homeostasis, and response to stress. The functions of de novo SL synthesis in vascular endothelial cells (EC), which line the entire circulatory system, are not well understood. Here we show that the EC de novo synthesis not only impacts vascular development but also maintains normal SL metabolic homeostasis in the circulatory system and peripheral organs. Mice with an endothelial-specific gene knockout of SPTLC1 (Sptlc1 ECKO), an essential subunit of the SPT complex, exhibited EC-intrinsic effects including reduced EC proliferation and tip/stalk cell differentiation, resulting in delayed retinal vascular development. In addition, Sptlc1 ECKO mice had reduced pathological retinal neovascularization in the oxygen-induced retinopathy model, suggesting that EC SL produced from the de novo pathway are needed for efficient VEGF signaling within the vascular system. Post-natal deletion of the EC Sptlc1also showed cell-extrinsic effects, including rapid reduction of several SL metabolites in plasma, red blood cells and peripheral organs (lung and liver) but not in the retina, part of the central nervous system (CNS). In the liver, EC de novo SL synthesis was required for acetaminophen-induced ceramide elevation and hepatotoxicity. These results suggest that EC-derived SL metabolites are in constant flux between the vasculature, circulatory elements, and parenchymal cells of non-CNS organs. Taken together, our data point to the central role of the endothelial SL biosynthesis in maintaining vascular development and neovascular proliferation, non-CNS tissue metabolic homeostasis and hepatocyte response to stress.

developmental biology↗
bioRxiv2021

Dynamics of repair and regeneration of adult zebrafish respiratory gill tissue after cryoinjury.

The study of respiratory tissue damage and repair is critical to understand not only the consequences of respiratory tissue exposure to infectious agents, irritants and toxic chemicals, but also to comprehend the pathogenesis of chronic inflammatory lung diseases. To gain further insights into these processes, we developed a gill cryoinjury model in the adult zebrafish. Time course analysis showed that cryoinjury of the gills triggered an inflammatory response, extensive cell death and collagen deposition at the site of injury. However, the inflammation was rapidly resolved, collagen accumulation dissipated and by 3 weeks after injury the affected gill tissue had begun to regenerate. RNA seq analysis of cryoinjured gills, combined with a comparison of zebrafish heart cryoinjury and caudal fin resection datasets, highlighted the differences and similarities of the transcriptional programmes deployed in response to injury in these three zebrafish models. Comparative RNA seq analysis of cryoinjured zebrafish gills with mouse pulmonary fibrosis datasets also identified target genes, including the understudied FIBIN, as differentially expressed in the two species. Further mining, including of human datasets, suggests that FIBIN may contribute to the successful resolution of tissue damage without fibrosis.

immunology↗
bioRxiv2020

Subcortical Atlas of the Rhesus Macaque (SARM) for Magnetic Resonance Imaging

Digitized neuroanatomical atlases are crucial for localizing brain structures and analyzing functional networks identified by magnetic resonance imaging (MRI). To aid in MRI data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. The structural scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM). The subcortical parcellation and nomenclature reflect those of the 4th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (RMBSC4; Paxinos et al., in preparation). The SARM features six parcellation levels, arranged hierarchically from fine regions-of-interest (ROIs) to broader composite regions, suited for fMRI studies. As a test, we ran a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques and found significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MR data processing software, such as AFNI, where the atlas can be embedded into the software alongside cortical macaque atlases. HighlightsO_LIWe present the Subcortical Atlas of the Rhesus Macaque (SARM). C_LIO_LISARM provides a neuroanatomical reference frame for neuroimaging analysis. C_LIO_LIThe entire subcortex is mapped, including the thalamus, basal ganglia, and brainstem. C_LIO_LIROIs are grouped hierarchically, making SARM useful at multiple spatial resolutions. C_LIO_LISARM is in the NMT v2 template space and complements the CHARM atlas for the cortex. C_LI

neuroscience↗
bioRxiv2020

Designing Sub-20 nm Nanocarriers for Small Molecule Delivery: Interplay among Structural Geometry, Assembly Energetics, and Cargo Release Kinetics

Biological constraints in diseased tissues have motivated the need for small nanocarriers (10-30 nm) to achieve sufficient vascular extravasation and pervasive tumor penetration. This particle size limit is only an order of magnitude larger than small molecules, such that cargo loading is better described by co-assembly processes rather than simple encapsulation. Understanding the structural, kinetic, and energetic contributions of carrier-cargo co-assembly is thus critical to achieve molecular-level control and predictable in vivo behavior. These interconnected set of properties were systematically examined using sub-20 nm self-assembled nanocarriers known as three-helix micelles (3HM). Both hydrophobicity and the "geometric packing parameter" dictate small molecule compatibility with 3HMs alkyl tail core. Planar obelisk-like apomorphine and doxorubicin (DOX) molecules intercalated well within the 3HM core and near the core-shell interface, forming an integral component to the co-assembly, as corroborated by small angle X-ray and neutron-scattering structural studies. DOX promoted crystalline alkyl tail ordering, which significantly increased (+63%) the activation energy of 3HM subunit exchange. Subsequently, 3HM-DOX displayed slow-release kinetics (t1/2=40 h) at physiological temperatures, with ~50x greater cargo preference for the micelle core as described by two drug partitioning coefficients (micellar core/shell Kp1 ~24, and shell/bulk solvent Kp2 ~2). The geometric and energetic insights between nanocarrier and their small molecule cargos developed here will aid in broader efforts to deconvolute the interconnected properties of carrier-drug co-assemblies, and to understand nanomedicine behavior throughout all the physical and in vivo processes they are intended to encounter.

bioengineering↗
bioRxiv2020

A comprehensive macaque fMRI pipeline and hierarchical atlas

Functional neuroimaging research in the non-human primate (NHP) has been advancing at a remarkable rate. The increase in available data establishes a need for robust analysis pipelines designed for NHP neuroimaging and accompanying template spaces to standardize the localization of neuroimaging results. Our group recently developed the NIMH Macaque Template (NMT), a high-resolution population average anatomical template and associated neuroimaging resources, providing researchers with a standard space for macaque neuroimaging (Seidlitz, Sponheim et al., 2018). Here, we release NMT v2, which includes both symmetric and asymmetric templates in stereotaxic orientation, with improvements in spatial contrast, processing efficiency, and segmentation. We also introduce the Cortical Hierarchy Atlas of the Rhesus Macaque (CHARM), a hierarchical parcellation of the macaque cerebral cortex with varying degrees of detail. These tools have been integrated into the neuroimaging analysis software AFNI (Cox, 1996) to provide a comprehensive and robust pipeline for fMRI processing, visualization and analysis of NHP data. AFNIs new @animal_warper program can be used to efficiently align anatomical scans to the NMT v2 space, and afni_proc.py integrates these results with full fMRI processing using macaque-specific parameters: from motion correction through regression modeling. Taken together, the NMT v2 and AFNI represent an all-in-one package for macaque functional neuroimaging analysis, as demonstrated with available demos for both task and resting state fMRI. HighlightsO_LIThe NMT v2, a stereotaxically aligned symmetric macaque template, is introduced. C_LIO_LIA new atlas (CHARM), defined on NMT v2, parcellates the cortex at six spatial scales. C_LIO_LIAFNIs @animal_warper aligns and maps data between monkey anatomicals and templates. C_LIO_LIAFNIs afni_proc.py facilitates monkey fMRI analysis with automated scripting and QC. C_LIO_LIDemos of macaque task and resting state fMRI analysis with these tools are provided. C_LI

neuroscience↗
bioRxiv2020

CIVET-Macaque: an automated pipeline for MRI-based cortical surface generation and cortical thickness in macaques

The MNI CIVET pipeline for automated extraction of cortical surfaces and evaluation of cortical thickness from in-vivo human MRI has been extended for processing macaque brains. Processing is performed based on the NIMH Macaque Template (NMT), as the reference template, with the anatomical parcellation of the surface following the D99 and CHARM atlases. The modifications needed to adapt CIVET to the macaque brain are detailed. Results have been obtained using CIVET-macaque to process the anatomical scans of the 31 macaques used to generate the NMT and another 95 macaques from the PRIME-DE initiative. It is anticipated that the open usage of CIVET-macaque will promote collaborative efforts in data collection and processing, sharing, and automated analyses from which the non-human primate brain imaging field will advance.

neuroscience↗
bioRxiv2020

A collaborative resource platform for non-human primate neuroimaging

Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field.

neuroscience↗
bioRxiv2020

Vacuolar sucrose homeostasis is critical for development, seed properties and survival of dark phases of Arabidopsis

Although we know that most of the cellular sucrose is present in the cytosol and vacuole, our knowledge on the impact of this sucrose compartmentation on plant properties is still fragmentary. Here we attempted to alter the intracellular sucrose compartmentation of Arabidopsis mesophyll cells by either, overexpression of the vacuolar sucrose loader BvTST2.1 or by generation of mutants with decreased vacuolar invertase activity (amiR vi1-2). Surprisingly, BvTST2.1 overexpression led to increased monosaccharide levels in leaves, while sucrose remained constant. Latter observation allows the conclusion, that vacuolar invertase activity in mesophyll vacuoles exceeds sucrose uptake in Arabidopsis, which gained independent support by analyses on tobacco leaves transiently overexpressing BvTST2.1 and the invertase inhibitor NbVIF. However, we observed strongly increased sucrose levels in leaf extracts from independent amiR vi1-2 lines and non-aqueous fractionations confirmed that sucrose accumulation in corresponding vacuoles. amiR vi1-2 lines exhibited impaired early development and decreased weight of seeds. When germinated in the dark, mutant seedlings showed problems to convert sucrose into monosaccharides. Cold temperatures induced marked downregulation of the expression of both VI genes, while frost tolerance of amiR vi1-2 mutants was similar to WT indicating that increased vacuolar sucrose levels fully compensate for low monosaccharide concentrations. HighlightVacuolar sucrose accumulation in Arabidopsis is limited by high invertase activity and disturbed vacuolar sucrose homeostasis impairs plant germination, development, seed properties and survival under darkness.

plant biology↗
bioRxiv2019

Low handgrip strength is closely associated with anemia among adults: A cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES)

BackgroundAnemia occurs because of insufficient hemoglobin, which provides oxygen to the body. Because of its close relationship with various illnesses, it must always be investigated clinically. Previous studies have demonstrated an association between hemoglobin concentration and handgrip strength. Thus, we aimed to analyze the association between handgrip strength and anemia in Korean adults to determine whether the handgrip strength test can be used as a tool to identify anemia.\n\nMethodsThe research subjects data were extracted from the 6th and 7th Korean National Health and Nutrition Examination Survey, between January 2013 and December 2017. Overall, data of 16,637 adults (weighted n= 9,734,598) were analyzed. Differences in sociodemographic factors (sex, age, education, income, and employment), lifestyle factors (alcohol consumption, smoking, and physical activity), and illness and health factors (body mass index, vitamin intake, iron intake, comorbid illnesses, and handgrip strength) by existence of anemia were analyzed using a chi square test. Binary logistic regression was performed to identify factors of anemia. Subgroup analysis, stratified by sex and age, was performed.\n\nResultsAmong Korean adults aged [≥] 19 years, 745,296 (7.7%) had anemia. Higher odds ratio (OR) of anemia occurred in the weak handgrip strength group compared to the strong handgrip strength group (OR=1.92, 95% CI: 1.58-2.33). The subgroup analysis showed a higher OR for anemia in the weak handgrip strength group than in the strong handgrip strength group, regardless of sex or age. However, the results showed that this association was greater for males (OR=2.13, 95% CI: 1.35-3.34) and for those aged [≥]65 years (OR=1.92, 95% CI: 1.42-2.58).\n\nConclusionThis study showed a strong association between handgrip strength and anemia, which was particularly strong for males and those aged [≥]65 years. Therefore, it is anticipated that handgrip strength can be used in anemia screening tests as a useful tool.

epidemiology↗
bioRxiv2019

Ultra-widefield fluorescein angiography findings in patients with multiple retinal holes.

PurposeTo evaluate the ultra-widefield fluorescein angiography (UWFA) findings in patients with multiple retinal holes.\n\nMethodsSeventy-five eyes, each with more than two retinal holes, underwent a comprehensive ophthalmologic examination, including UWFA, along with 77 age-matched control eyes with no retinal holes. The UWFA was scored according to a system suggested by the Angiography Scoring for Uveitis Working Group (ASUWG). UWFA findings from the patients with retinal holes were compared with those of the control group without retinal holes. Factors associated with a high ASUWG score were also evaluated.\n\nResultsPatients with multiple retinal holes showed a significantly higher prevalence of retinal vascular staining/leakage, capillary leakage at the posterior pole, and capillary leakage at the periphery when compared to the control group (p<0.001, for each of them). Univariate analysis revealed that logMAR BCVA (r=0.271, p=0.027), spherical equivalent (r= -0.275, p=0.021), and number of retinal holes (r=0.271, p=0.027) were associated with a higher ASUWG score. After adjustments for age, gender, and logMAR BCVA, multivariate regression analysis revealed that the spherical equivalent was independently associated with a higher ASUWG score (r2=0.161, p=0.001).\n\nConclusionsPatients with multiple retinal holes showed profound peripheral vascular leakages on UWFA findings, suggesting the presence of chronic retinal traction induced by equatorial scleral elongation.

neuroscience↗
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↗
bioRxiv2017

An open resource for nonhuman primate imaging

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience.\n\nUnfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMate Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 13 independent data collections aggregated across 11 sites (total = 98 macaque monkeys). We also outline the unique pitfalls and challenges that should be considered in the analysis of the non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

neuroscience↗