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Biology subjects

Park, G. Y.

Publications and source records attributed to Park, G. Y..

4 recordsLinked to original sources

Spatial Mapping of the Lung Cancer Ecosystem Reveals Distinct Patterns of Intratumoral and Internodular Heterogeneity

The spatial organization of malignant and non-malignant cells within the tumor microenvironment (TME) critically influences tumor evolution and therapeutic response. However, the architecture of micro-niches remains incompletely understood. Leveraging Xenium-based spatial transcriptomics, we comprehensively mapped the spatial ecosystem of an orthotopic murine lung cancer model, identifying distinct spatial domains that form unique, organized cellular neighborhoods. These domains cluster into three major communities: (1) non-tumoral regions that recapitulate canonical normal lung structures; (2) a heterogeneous peri-tumoral region composed of spatial domains characterized by mesenchymal remodeling, active immune checkpoint signaling, and immunosuppressive myeloid populations; and (3) intra-tumoral regions that reveal marked tumor nodule heterogeneity, with unique tumor-specific domains exhibiting hallmark cancer pathways. Furthermore, our analytic approach was applicable to human lung cancer tissue. Notably, spatial domain analysis allowed us to resolve tumor nodules into multiple biologically distinct subtypes, defined by domain composition, hallmark cancer programs, and intercellular communication patterns within the TME.

cancer biology↗

Effect of the daily exposure of 1.7 GHz LTE electromagnetic field in early fetal brain development using a human brain organoid model of the cerebral cortex

Wireless communication technologys ubiquity means constant exposure to radiofrequency electromagnetic fields (RF-EMF). While concerns exist about RF-EMFs effects on fetal brain development, studying this in pregnant women poses ethical and safety challenges. Our study examined 1.7 GHz LTE RF-EMFs impact on early human fetal brain development using brain organoids derived from human induced pluripotent stem cells (hiPSCs). Previous research showed that 100-day-old human cerebral cortical brain organoids correspond to 19-24 weeks post-conception of fetal brain development. We exposed organoids to 1.7 GHz LTE RF-EMF at 8 W/kg specific absorption rate (SAR) for 5 hours daily up to 100 days. We monitored size, developmental morphology, and developmental stage markers using immunofluorescence microscopy and qPCR analysis. Comparing RF-EMF-exposed organoids with controls showed no significant differences in size, development, or expression of key markers: SOX2 and PAX6 (pluripotent cell markers), NEUN (mature neuronal marker), MAP2 (dendrite marker), and SYN1 (synapse marker). Results suggest that daily exposure to 1.7 GHz LTE RF-EMF at 8 W/kg SAR may not significantly affect early human fetal brain development.

developmental biology↗

Oxo-M and 4-PPBP Delivery via Multi-Domain Peptide Hydrogel Toward Tendon Regeneration

We have recently identified novel small molecules, Oxo-M and 4-PPBP, which specifically stimulates endogenous tendon stem/progenitor cells (TSCs) leading to potential regenerative healing of fully-transected tendons. Here we investigated an injectable, multi-domain peptide (MDP) hydrogel providing a controlled delivery of the small molecules for regenerative tendon healing. We investigated the release kinetics of Oxo-M and 4-PPBP from MDP hydrogels and the effect of MDP-released small molecules on tenogenic differentiation of TSCs and in vivo tendon healing. In vitro, MDP showed a sustained release of Oxo-M and 4-PPBP and a slower degradation compared to fibrin. In addition, tenogenic gene expression was significantly increased in TSC with MDP-released Oxo-M and 4-PPBP as compared to the fibrin-released. In vivo, MDP releasing Oxo-M and 4-PPBP significantly improved tendon healing, likely associated with prolonged effects of Oxo-M and 4-PPBP on suppression of M1 macrophages and promotion of M2 macrophages. Comprehensive analyses including histomorphology, digital image processing, and modulus mapping with nanoindentation consistently suggested that Oxo-M and 4-PPBP delivered via MDP further improved tendon healing as compared to fibrin-based delivery. In conclusion, MDP delivered with Oxo-M and 4-PPBP may serve as an efficient regenerative therapeutic for in situ tendon regeneration and healing.

bioengineering↗

Task complexity interacts with state-space uncertainty in the arbitration process between model-based and model-free reinforcement-learning at both behavioral and neural levels

A major open question concerns how the brain governs the allocation of control between two distinct strategies for learning from reinforcement: model-based and model-free reinforcement learning. While there is evidence to suggest that the reliability of the predictions of the two systems is a key variable responsible for the arbitration process, another key variable has remained relatively unexplored: the role of task complexity. By using a combination of novel task design, computational modeling, and model-based fMRI analysis, we examined the role of task complexity alongside state-space uncertainty in the arbitration process between model-based and model-free RL. We found evidence to suggest that task complexity plays a role in influencing the arbitration process alongside state-space uncertainty. Participants tended to increase model-based RL control in response to increasing task complexity. However, they resorted to model-free RL when both uncertainty and task complexity were high, suggesting that these two variables interact during the arbitration process. Computational fMRI revealed that task complexity interacts with neural representations of the reliability of the two systems in the inferior prefrontal cortex bilaterally. These findings provide insight into how the inferior prefrontal cortex negotiates the trade-off between model-based and model-free RL in the presence of uncertainty and complexity, and more generally, illustrates how the brain resolves uncertainty and complexity in dynamically changing environments.\n\nSUMMARY OF FINDINGS- Elucidated the role of state-space uncertainty and complexity in model-based and model-free RL.\n\n- Found behavioral and neural evidence for complexity-sensitive prefrontal arbitration.\n\n- High task complexity induces explorative model-based RL.

neuroscience↗