Biology subjects

Oh, K.

Publications and source records attributed to Oh, K..

10 recordsLinked to original sources

bioRxiv2026

Slower cardiac-coupled cortical dynamics link depressive symptoms to inflexible affective updating

Depression is marked by blunted affective responses to context, which interoceptive accounts trace to altered neural representations of bodily states. Yet this evidence mainly concerns response magnitude, not how quickly affect is updated when contexts change. Here we tested whether depressive symptom severity is related to delayed affective updating, and whether cortical dynamics tracking cardiac states account for this delay. To this end, we applied a movie-watching paradigm with independently defined contextual shifts, continuous affect ratings, electroencephalography, and electrocardiography in individuals spanning a continuum of depressive symptoms. Combining deep representation learning and a dynamical systems framework, we quantified how quickly (speed) and how sharply (angle) cardiac-coupled cortical representations reorganized at each shift. Greater symptom severity predicted longer latency to enter the context-congruent affective state across contextual shifts, regardless of valence. In a cross-sectional mediation analysis, slower speed, but not angle, accounted for this association. This mediation was specific to depressive symptoms, contextual shifts, and cardiac-coupled neural dynamics. These findings extend the embodied account of depression from blunted affective intensity toward its inflexible updating at moments of contextual shift, and offer a broadly applicable framework for quantifying brain-body dynamics across affective dysfunctions.

neuroscience↗

bioRxiv2026

VISUAL EXPERIENCE SHAPES ARM POSITION SENSE IN INTERNAL AND EXTERNAL REFERENCE FRAMES AND ASSOCIATED CORTICAL LOAD

The ability to accurately perceive arm position is essential for motor control and depends on the integration of proprioceptive and visual information. However, how lifelong visual impairment (VI) affects position sense and its neural correlates remains unclear. We quantified arm position sense and associated cognitive-motor load in right-handed visually impaired (n = 7) and normally sighted (NS; n = 7) individuals using three bilateral arm position matching tasks: joint angle matching (JAM; internal coordinates), hand direction-distance matching (DDM; external coordinates), and mirror direction-distance matching (MDDM; external coordinates kinematically identical to JAM). Cognitive load was assessed using the contingent negative variation (CNV) from EEG recordings. VI participants exhibited reduced accuracy and precision of arm position sense in most conditions, and greater CNV magnitude, particularly in the left parietal cortex. Across both groups, performance was worse and CNV magnitude was greater in the DDM task compared with JAM, whereas JAM and MDDM yielded similar behavioral and neural outcomes. These findings indicate that (i) visual experience enhances arm position sense, and (ii) representing limb position in external coordinates imposes greater cognitive demands than encoding joint-based posture. The similarity between JAM and MDDM suggests that participants preferentially rely on internal representations when task kinematics permit.

neuroscience↗

bioRxiv2024

Sensitivity of Cerebellar Reaching Ataxia to Kinematic and Dynamic Demands

Individuals with cerebellar ataxia face significant challenges in controlling reaching, especially when multi-joint movements are involved. This study investigated the effects of kinematic and dynamic demands on reaching using a home-based virtual reality task. Participants with and without cerebellar ataxia reached to target locations designed to elicit a range of coordination strategies between shoulder and elbow joint movements. Compared with control subjects, cerebellar subjects presented greater initial reaching direction errors, larger hand trajectory curvatures, and more variability. Kinematic simulations indicated that early hand movement errors were sensitive to the required onset times and rates of joint movements and were most impaired when opposite direction joint movements were required (e.g., elbow extension with shoulder flexion). Dynamic analysis revealed that cerebellar participants movements were more impaired in reaching directions where interaction torques would normally assist the desired elbow and shoulder movements. These reach directions were also those that required joint movements in opposite directions. Overall, our data suggest that reaching deficits in cerebellar ataxia result from 1) the early-phase motion planning deficits that are exacerbated by stringent timing coordination requirements and 2) the inability to compensate for interaction torques, particularly when they assist the intended movement.

neuroscience↗

bioRxiv2024

Wirelessly-Powered Ingestible Electronic Capsule for Non-invasive Gastrointestinal Optogenetics

Optogenetics enables the activation and inhibition of neurons with cell specificity. The gut harbors intricate networks of enteric and central neurons. Uncovering these neuronal pathways in vivo is challenging with traditional neuroscience probes due to the highly motile and harsh gut environment. Here we report the development of an ingestible electronic capsule for non-invasive optical gut stimulation (ICOPS) in rodents. ICOPS is powered wirelessly via a transmitter coil, dosed via oral gavage, and safely excreted without causing obstruction. ICOPS permits modular interchangeability of onboard light-emitting diodes (LEDs) for illumination. We exemplify this with optical irradiance at 470 nm, a commonly-used wavelength in optogenetics for activating channelrhodopsin2. ICOPS features a micro-LED ({micro}LED), a 460-turn coil wound around a ferrite core, and a resonating capacitor. We optimized the transmitting and receiving circuits to achieve maximum power transfer at low operating frequencies (45-140 kHz), overcoming challenges like loose coupling and misalignment. The capsule operates effectively at a distance up to 12 cm longitudinally, 9 cm laterally, and 75{degrees} rotational angle relative to the magnetic field. Specific absorption rate (SAR) calculations indicate transmitter-induced SAR levels within safe limits for the occupational environment at 6 Arms and 45 and 63 kHz frequencies ICOPS is robust and transits through the rat gastrointestinal (GI) tract in under 20 hours intact. We demonstrate in vivo functionality and viability of ICOPS using IVIS micro-computed tomography ({micro}CT). ICOPS could pave the way for non-invasive optogenetic interfacing of enteric neural circuits towards their use to regulate motility, visceral pain, and other gastrointestinal disorders.

bioengineering↗

bioRxiv2024

A genome-wide association study of high-sensitivity C-reactive protein in a large Korean population highlights its role in cholesterol metabolism

High-sensitivity C-reactive protein (hsCRP) is a representative biomarker of systemic inflammation and is associated with numerous complex diseases. To explore the biological pathways and functions underlying chronic inflammation, we conducted a genome-wide association study (GWAS) and several post-GWAS analyses of the hsCRP levels. This study was performed on data from 71,019 Koreans and is one of the largest East Asian studies. Overall, 69 independent single nucleotide polymorphisms (SNPs) were identified, including 12 novel variants located within SHE, RP11-740C1.2, FCRL6, STEAP1B, AC002480.5, TOMM7, SPPL3, RP11-216P16.6, RP11-209K10.2, CTC-490E21.12, CYP2F2P, CBLC, and PVRL2. The implicated genes and pathways are primarily involved in cholesterol metabolism and the immune response. A phenome-wide association study was performed based on a polygenic risk score constructed using 69 hsCRP-associated SNPs. Notably, the alleles associated with higher hsCRP levels appeared to be associated with lower low-density lipoprotein cholesterol levels (P=1.69 x 10-33, {beta}=-1.47). Our findings provide evidence of a link between hsCRP and cholesterol as well as the clinical importance of hsCRP. Specifically, we suggest that genetically determined hsCRP levels may be useful for predicting the potential risk of cardiovascular or other diseases related to lipid metabolism. Authors summaryChronic inflammation is associated with numerous complex diseases, including cancer, cardiovascular disease, and diabetes. Previous studies have shown that East Asians have lower levels of C-reactive protein (CRP), a biomarker of inflammation, than other ancestry groups. To identify East Asian-specific single nucleotide polymorphisms (SNPs) associated with chronic inflammation, we conducted a genome-wide association study and secondary genetic analyses on hsCRP in 71,019 Korean individuals. In total, 69 SNPs were identified, of which 12 were novel. A majority of the identified SNPs are located within genes (LEPR, IL6R, and APOE) that are involved in cholesterol metabolism and immune response. Notably, we found genetically determined hsCRP level may contribute to decrease cholesterol level, in contrast to previous epidemiological studies. Therefore, we suggest genetically determined hsCRP as a clinical tool for predicting the potential risk of abnormal cholesterol metabolism and its related diseases.

genomics↗

bioRxiv2023

Structural and functional vascular dysfunction within brain metastases is linked to pembrolizumab inefficacy

Structurally and functionally aberrant vasculature is a hallmark of tumor angiogenesis and treatment resistance. Given the synergistic link between aberrant tumor vasculature and immunosuppression, we analyzed perfusion MRI for 44 patients with brain metastases (BM) undergoing treatment with pembrolizumab. To date, vascular-immune communication, or the relationship between immune checkpoint inhibitor (ICI) efficacy and vascular architecture, has not been well-characterized in human imaging studies. We found that ICI-responsive BM possessed a structurally balanced vascular makeup, which was linked to improved vascular efficiency and an immune-stimulatory microenvironment. In contrast, ICI-resistant BM were characterized by a lack of immune cell infiltration and a highly aberrant vasculature dominated by large-caliber vessels. Peri-tumor region analysis revealed early functional changes predictive of ICI resistance before radiographic evidence on conventional MRI. This study was one of the largest functional imaging studies for BM and establishes a foundation for functional studies that illuminate the mechanisms linking patterns of vascular architecture with immunosuppression, as targeting these aspects of cancer biology may serve as the basis for future combination treatments.

cancer biology↗

bioRxiv2021

Improving Lab Culture Through Self-Assessment: A Case Study

PurposeMotivated by perceived dissatisfaction within our labs changed working environment brought about by the COVID-19 pandemic, we performed a self-assessment of our lab culture through anonymous surveys and live sessions. MethodsIn Survey 1, we asked each lab member to identify and rank up to 10 values that are important for a healthy lab environment. They were then asked to rate how well the lab embodied those values at two time points: before the COVID-19 pandemic while working onsite, and at the time of the survey while working remotely (10 months into the pandemic). In a series of live group sessions, we reviewed relevant literature and the survey results to finalize ten themes. We then reflected on each theme and proposed action items to address any deficiencies. Finally, we conducted Survey 2 after the self-assessment to judge the groups finalized themes, implemented changes, and overall satisfaction with the assessment process. ResultsThemes identified were attitude, accountability, teamwork/collaboration, communication, diversity/inclusion, emotional intelligence, integrity, training, well-being, and adaptability in crisis-management. All lab members liked the self-assessment process and felt their voices were heard. On average, there was a 12% increase in satisfaction across all themes from the start to end of the lab assessment. ConclusionWe successfully assessed the culture of our lab and subsequently improved lab member satisfaction. The success of this team project suggests that other scientific labs could benefit from similar interactive self-assessments.

scientific communication and education↗

bioRxiv2020

A Microglial Subset at the Tumor-Stroma Interface of Glioma

BackgroundMyeloid involvement in High Grade Gliomas, such as Glioblastoma, has become apparent and detrimental to disease outcomes. There is great interest in characterizing the HGG tumor microenvironment to understand how neoplastic lesions are supported, and to devise novel therapeutic targets. The tumor microenvironment of the central nervous system is unique as it contains neural and specialized glial cells, including the resident myeloid cells, microglia. Glioma-associated microglia and peripherally infiltrating monocytes/macrophages (GAM) accumulate within the neoplastic lesion where they facilitate tumor growth and drive immunosuppression. A longstanding limitation has been the ability to accurately differentiate microglia and macrophage roles in pathology, and identify the consequences of the spatial organization of these cells. ResultsHere we characterize the tumor-stroma border and identify peripheral glioma-associated microglia (PGAM) at the tumor leading edge as a unique subpopulation of GAM. Using data mining and analyses of samples derived from both murine and human sources, we show that PGAM exhibit a pro-inflammatory and chemotactic phenotype that is associated with peripheral monocyte recruitment, poorly enhancing radiomic features, and decreased overall survival. ConclusionsPGAM act as a unique subset of GAM, at the tumor-stroma interface, corresponding to disease outcomes. We propose the application of a novel gene signature to identify these cells, and suggest that PGAM constitute a cellular target of the TME. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/357459v1_ufig1.gif" ALT="Figure 1"> View larger version (76K): org.highwire.dtl.DTLVardef@6c08b6org.highwire.dtl.DTLVardef@b01421org.highwire.dtl.DTLVardef@1f99f9aorg.highwire.dtl.DTLVardef@15d5011_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

A Combinatorial Approach of Biparental QTL Mapping and Genome-Wide Association Analysis Identifies Candidate Genes for Phytophthora Blight Resistance in Sesame

Phytophthora blight, caused by pathogen Phytophthora nicotianae, is responsible for a huge reduction in sesame (Sesamum indicum L.) crop yields. In this study, we utilized a combinatorial approach involving biparental QTL mapping and genome-wide association (GWAS) analysis to identify genes associated with Phytophthora blight resistance in sesame. Evaluation of resistant of the parental varieties (Goenbaek, Osan and Milsung) and the RILs of both the populations in greenhouse conditions suggested the qualitative nature of the trait.. The genetic map comprised thirteen LGs covering a total map length of 887.49 cM with an average inter-marker distance of 4.69 cM. Significant QTLs explaining phenotypic variation in the range of 2.25% to 69.24% were identified on chromosomes 10 and 13 (Chr10 and Chr13). A resistance locus detected on Chr10 was found to be highly significant. The association of this locus to PBR was also identified through BSA and single marker analysis in Goenbaek x Milsung cross and through genome-wide association mapping of 87 sesame accessions. The GWAS analysis identified 44 SNP loci significantly associated with Phytophthora disease-resistant traits on Chr10. Further, the haplotype block analysis conducted in order to find whether the SNPs associated with resistance in this study showed that the SNPs are in high LD with the resistance QTL. We obtained a total of 68 candidate genes, which included a number of defense-related R genes. One of the genes, SIN_1019016 (At1g58390) showed high expression in the resistant parent. The results from this study would be highly useful in identifying genetic and molecular factors associated with Phytophthora blight resistance in sesame.

molecular biology↗

bioRxiv2019

Locally Fixed Alleles: A method to localize gene drive to island populations

Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the \"Locally Fixed Alleles\" approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to multiple genomic alleles becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.

evolutionary biology↗