Biology subjects

Yoo, H. J.

Publications and source records attributed to Yoo, H. J..

9 recordsLinked to original sources

bioRxiv2026

In-vivo MRI of noradrenergic and dopaminergic nuclei predicts future cognition and Alzheimers disease progression

Noradrenergic and dopaminergic nuclei modulate cognition, and post-mortem data indicate they are affected early in the neurodegenerative cascade of Alzheimers disease. We derived in-vivo locus coeruleus (LC) and substantia nigra-ventral tegmental area (SN-VTA) MRI integrity measures from 739 ADNI participants, examined MRI-histology correspondence in individuals with both in-vivo imaging and post-mortem data, and tested whether these measures reflect early MRI-indexed degeneration predicting later cognitive decline. LC and SN-VTA contrast predicted cognitive and behavioral function 10 years later, despite only weak associations with current function. LC- and SN-VTA-associated brain-wide atrophy patterns aligned with PET-derived norepinephrine-transporter and dopamine-receptor maps, respectively. A one-standard-deviation decrease in baseline LC contrast was associated with 84% higher five-year odds of MCI-to-AD progression, and predictive effects of the catecholaminergic nuclei were mediated by their corresponding atrophy patterns. The SN-VTA pattern was associated with less amyloid PET-related memory decline. Together, these findings establish LC and SN-VTA MRI contrast as markers of early neurodegeneration that forecast cognitive decline years before clinical onset.

neuroscience↗

bioRxiv2026

AI-driven framework modeling perturbation in brain organoids reveals candidate genes for autism

Autism gene discovery is constrained by the rarity and heterogeneity of damaging variants, requiring large cohorts to identify susceptibility genes. Neural organoids and single-cell foundation models enable perturbation modeling in neurodevelopmental contexts. Here, we show that perturbation-informed foundation modeling of neural organoids can provide functional context for prioritizing candidate genes with genomic and clinical support. We constructed a 3.6-million-cell organoid atlas and trained models to predict genome-wide perturbation responses. Benchmarking 17 models identified a telencephalic neuron-specific model best preserving autism-relevant perturbation structure. Genome-wide profiling revealed two clusters associated with mid-fetal synaptic neuronal processes and early radial glia ubiquitin signaling. These clusters were supported by damaging-variant enrichment and clinical phenotypes across 89,916 family-based samples. Logistic-regression prioritization identified 343 candidates, including 167 in the key clusters, with convergence across TADA signals and recurrent evidence for NBEA and KLHDC10. This framework integrates predicted perturbation effects with genomic evidence to support autism candidate prioritization.

bioinformatics↗

bioRxiv2026

Distinct Neural Systems Supporting Afferent and Efferent Autonomic Activity

Numerous studies have reported brain correlates of autonomic activity. However, ambiguity exists regarding whether those correlates reflect receiving or sending out autonomic signals. Additionally, little is known about how emotion and aging interact with brain-autonomic coordination. Based on time-varying heart rate variability (HRV) and blood oxygenation level dependent (BOLD) data (N = 104 younger; N = 51 older adults), we found insular and cingulate activity was negatively correlated with HRV during emotion regulation. We further examined the afferent and efferent nature of HRV-BOLD correlations during rest (N = 102 younger; N = 51 older adults). Functionally afferent regions where decreases in HRV were associated with subsequently increased BOLD activity included the posterior insula, postcentral gyrus and frontal pole. Functionally efferent regions where increased activity was associated with subsequently increased HRV included the anterior insula and cingulate. Information appeared to flow in one direction as the afferent regions activity Granger-predicted the efferent regions activity. Together, our findings suggest a feedback loop where decreased HRV increases the afferent regions activity, which activates the efferent regions, leading to increased HRV. Aging seems to affect this system; the efferent and afferent regions scarcely overlapped for younger adults, but did overlap for older adults.

neuroscience↗

bioRxiv2025

Effects of different slow paced breathing regimes on cerebrospinal fluid (CSF) oscillations

Cerebrospinal fluid (CSF) transport is crucial for clearing waste from the brain and is largely driven by blood vessel oscillatory dynamics. During non-REM sleep, large oscillations occur in the infraslow range around 0.02-0.03 Hz, where noradrenergically driven vasomotion, blood volume and CSF flow are tightly coupled. Whether an infraslow oscillation induced by respiration can engage comparable dynamics during wakefulness is unknown. Utilizing a fast neuroimaging technique, we investigated the effects of four different slow paced respiratory conditions on CSF oscillations in 35 healthy adults (aged 18-30): paced breathing at 0.09-0.11 Hz and 0.05-0.07 Hz, and paced sighing at 0.05-0.07 Hz and 0.02-0.03 Hz. All four conditions increased respiratory volume, low-frequency respiratory power, CSF oscillatory power and BOLD global signal amplitude relative to rest, and CSF power did not differ among them. However, the infraslow slow sighing produced significantly higher CSF-BOLD coupling than all the other conditions, together with the largest global signal amplitude, an index associated with reduced arousal. This effect of infraslow sighing was not linked with respiratory power, as paced breathing at 0.05-0.07 Hz had the greatest respiratory power yet the weakest CSF-BOLD coupling, falling below rest. Cardiac spectral power was also lower during infraslow sighing than during any other breathing manipulation. Stimulating oscillatory dynamics via respiration during wakefulness therefore may recruit neurovascular-CSF coupling due to the same infraslow-specific dynamics that are believed to drive sleep-dependent waste clearance. Our study provides evidence that slow paced breathing increases CSF oscillations during wakefulness. Furthermore, we found that sighing at the frequency of the infraslow band linked to glymphatic clearance increases the coupling between blood and CSF dynamics.

neuroscience↗

bioRxiv2025

Biomarker Discovery via Integrative Multi-omics for Children exposed to Humidifier Disinfectant

RationaleExposure to humidifier disinfectants has been linked to an array of pulmonary disorders and diminished lung functionality particularly reduced Forced Vital Capacity (FVC). ObjectivesThis investigation sought to identify diagnostic biomarkers for early detection of children at elevated risk of developing chronic respiratory conditions following such exposure. MethodsOur research employed a comprehensive multi-omics strategy analyzing 70 pediatric patients alongside 10 controls, seamlessly integrating clinical assessments with transcriptomics, methylomics, proteomics, and metabolomics data. The analytical framework utilized a sophisticated combination of Non-negative Matrix Factorization (NMF), Multi-Omics Factor Analysis (MOFA), and advanced machine learning algorithms. Measurements and Main ResultsNMF clustering uncovered distinctive protein expression patterns associated with integrin-mediated signaling pathways and immune response mechanisms. Complementarily, MOFA identified latent factors correlating with lung function metrics, highlighting critical molecular pathways involved in integrin cell surface interactions and lipid metabolism regulation. Machine learning-based analysis facilitated the development of a multi-marker panel-comprising IGHV2-70, LysoPC (16:0), and hexadecyl ferulate-which achieved 81.46% accuracy in identifying pulmonary dysfunction cohort. ConclusionsThese findings suggest that alterations in integrin-related signaling networks and dysregulation of lipid metabolism play pivotal roles in mediating the long-term pulmonary consequences of humidifier disinfectant exposure. The proposed multi-marker panel offers significant potential for enhanced risk stratification and timely therapeutic intervention. At a Glance CommentaryO_ST_ABSScientific Knowledge on the SubjectC_ST_ABSExtensive epidemiological evidence has established the causal relationship between humidifier disinfectant exposure and pulmonary dysfunction; however, clinically validated biomarkers for predicting chronic lung disease progression remain limited. Pediatric populations demonstrate unique pathophysiological mechanisms distinct from adults, highlighting the critical necessity for biomarker identification grounded in comprehensive molecular understanding. Despite advances in omics technologies, recent investigations have encountered significant obstacles in achieving deeper mechanistic insights, predominantly attributable to methodological constraints in harmonizing clinical phenotypes with high-dimensional molecular datasets. What This Study Adds to the FieldThis investigation elucidates the fundamental contributions of integrin-mediated signaling cascades and lipid metabolic networks to persistent pulmonary dysfunction following humidifier disinfectant exposure. Our analyses revealed coordinated regulation of integrin signaling pathways and immune response networks through NMF clustering, indicating dynamic temporal evolution of inflammatory responses during chronic disease progression, with temporally distinct molecular signatures identified across discrete observation intervals. Multi-omics factor analysis (MOFA) corroborated integrin pathway dysregulation while additionally uncovering systematic suppression of lipid metabolic processes. Furthermore, machine learning algorithms enabled development of a robust three-component biomarker panel--encompassing IGHV2-70, LysoPC (16:0), and hexadecyl ferulate--demonstrating 81.46% classification accuracy for pulmonary dysfunction phenotypes. Collectively, these findings substantially advance mechanistic understanding of chronic lung injury in vulnerable pediatric cohorts and identify clinically relevant biomarkers with translational potential for risk stratification and therapeutic targeting in clinical practice.

systems biology↗

bioRxiv2025

The Physiological Component of the BOLD Signal: Impact of Age and Heart Rate Variability Biofeedback Training

Aging is associated with declines in autonomic nervous system (ANS) function, including reduced heart rate variability (HRV), impaired neurovascular coupling, and diminished cerebrovascular responsiveness--factors that may contribute to cognitive decline and neurodegenerative diseases. Understanding how aging alters physiological signal integration in the brain is crucial for identifying potential interventions to promote brain health. This study examines age-related differences in how cardiac and respiratory fluctuations influence the blood oxygenation level-dependent (BOLD) signal, using two independent resting-state fMRI datasets with concurrent physiological recordings from younger and older adults. Our findings reveal significant age-related reductions in the percent variance of the BOLD signal explained by heart rate (HR), respiratory variation (RV), and end-tidal CO2, particularly in regions involved in autonomic regulation, including the orbitofrontal cortex, anterior cingulate cortex, insula, basal ganglia, and white matter. Cross-correlation analysis also revealed that younger adults exhibited stronger HR-BOLD coupling in white matter, as well as a more rapid BOLD response to RV and CO2 in gray matter. Additionally, we investigated the effects of heart rate variability biofeedback (HRV-BF) training, a non-invasive intervention designed to modulate heart rate oscillations. The intervention altered physiological-BOLD coupling in an age- and training-dependent manner: older adults who underwent HRV-BF to enhance HR oscillations exhibited a shift toward younger-like HR-BOLD coupling patterns, while younger adults who trained to suppress HR oscillations showed increased CO2-BOLD coupling. These findings suggest that HRV-BF may help mitigate age-related declines in autonomic or cerebrovascular function. Overall, this study underscores the role of physiological dynamics in brain aging and highlights the importance of considering autonomic function when interpreting BOLD signals. By demonstrating that HRV-BF can modulate physiological-BOLD interactions, our findings suggest a potential pathway for enhancing cerebrovascular function and preserving brain health across the lifespan.

neuroscience↗

bioRxiv2023

De novo fatty-acid synthesis protects invariant NKT cells from cell death, thereby promoting their homeostasis and pathogenic roles in airway hyperresponsiveness

AbstractInvariant natural-killer T (iNKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this in iNKT cells is very limited. It is also not clear whether such metabolic regulation of iNKT cells could participate in their pathogenic activities in asthma. Here, we showed that acetyl-coA-carboxylase 1 (ACC1)-mediated de novo fatty-acid synthesis is required for the survival of iNKT cells and their deleterious functions in allergic asthma. ACC1, which is a key fatty-acid synthesis enzyme, was highly expressed by lung iNKT cells from WT mice that were developing asthma. Cd4-CreAcc1fl/fl mice failed to develop OVA-induced and HDM-induced asthma. Moreover, iNKT cell-deficient mice that were reconstituted with ACC1-deficient iNKT cells failed to develop asthma, unlike when WT iNKT cells were transferred. ACC1 deficiency in iNKT cells associated with reduced expression of fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR){gamma}, but increased glycolytic capacity that promoted iNKT-cell death. Furthermore, circulating iNKT cells from allergic-asthma patients expressed higher ACC1 and PPARG levels than the corresponding cells from non-allergic-asthma patients and healthy individuals. Thus, de novo fatty-acid synthesis prevents iNKT-cell death via an ACC1-FABP-PPAR{gamma} axis, which contributes to their homeostasis and their pathogenic roles in allergic asthma.

immunology↗

bioRxiv2021

Emotion Down- and Up-Regulation Act on Spatially Distinct Brain Areas:Interoceptive Regions to Calm Down and Other Affective Regions to Amp Up

Prior studies on emotion regulation identified a set of brain regions specialized for generating and controlling affect. Researchers generally agree that when up- and down-regulating emotion, control regions in the prefrontal cortex turn up or down activity in affect-generating areas. However, the assumption that turning up and down emotions produces opposite effects in the same affect-generating regions is untested. We call this assumption the affective dial hypothesis. Our study tested this hypothesis by examining the overlap between the sets of regions activated during up-regulation and those deactivated during down-regulation in a large number of participants (N=105). We found that up- and down-regulation both recruit regulatory regions such as the inferior frontal gyrus and dorsal anterior cingulate gyrus but act on distinct affect-generating regions. While up-regulation increases BOLD signal in regions associated with emotion such as the amygdala, anterior insula, striatum and anterior cingulate gyrus as well as in regions associated with sympathetic vascular activity such as periventricular white matter, down-regulation decreases signal in regions receiving interoceptive input such as the posterior insula and postcentral gyrus. These findings indicate that up- and down-regulation do not generally exert opposing effects on the same affect-generating regions. Instead, they target different brain circuits. Significance StatementMany contexts require modulating ones own emotions. Identifying the brain areas implementing these regulatory processes should advance understanding emotional disorders and designing potential interventions. The emotion regulation field has an implicit assumption we call the affective dial hypothesis: that both emotion up- and down-regulation modulate the same emotion-generating brain areas. Countering the hypothesis, our findings indicate that up- and down-modulating emotions target different brain areas. Thus, the mechanisms underlying emotion regulation differ more than previously appreciated for up- versus down-regulation. In addition to their theoretical importance, these findings are critical for researchers attempting to target activity in particular brain regions during an emotion regulation intervention.

neuroscience↗

bioRxiv2019

Noncoding de novo mutations contribute to autism spectrum disorder via chromatin interactions

Three-dimensional chromatin structures regulate gene expression across genome. The significance of de novo mutations (DNMs) affecting chromatin interactions in autism spectrum disorder (ASD) remains poorly understood. We generated 931 whole-genome sequences for Korean simplex families to detect DNMs and identified target genes dysregulated by noncoding DNMs via long-range chromatin interactions between regulatory elements. Notably, noncoding DNMs that affect chromatin interactions exhibited transcriptional dysregulation implicated in ASD risks. Correspondingly, target genes were significantly involved in histone modification, prenatal brain development, and pregnancy. Both noncoding and coding DNMs collectively contributed to low IQ in ASD. Indeed, noncoding DNMs resulted in alterations, via chromatin interactions, in target gene expression in primitive neural stem cells derived from human induced pluripotent stem cells from an ASD subject. The emerging neurodevelopmental genes, not previously implicated in ASD, include CTNNA2, GRB10, IKZF1, PDE3B, and BACE1. Our results were reproducible in 517 probands from MSSNG cohort. This work demonstrates that noncoding DNMs contribute to ASD via chromatin interactions.

neuroscience↗