Biology subjects

Lee, J.-I.

Publications and source records attributed to Lee, J.-I..

4 recordsLinked to original sources

bioRxiv2026

Revisiting Analog Electrical Stimulation with Current Focusing in a Guinea Pig Model of Cochlear Implants.

Modern cochlear implants (CIs) use pulsatile stimulation to restore hearing for individuals with severe hearing loss. CIs provide robust speech recognition in quiet but poorly represent temporal fine structure (TFS), needed for challenging listening situations. Analog stimulation preserves the acoustic waveform and may better encode TFS, yet it has not been evaluated combined with modern current-focusing strategies. We compared neural responses in the inferior colliculus (IC) evoked by CI stimuli consisting of 100 pulses/s biphasic pulse trains and 100 cycles/s sinusoidal analog stimulation with monopolar, bipolar, and tripolar electrode configurations in urethane-anesthetized guinea pigs. Following cochlear implantation, multiunit activity was recorded from the tonotopic axis of the central nucleus of the IC using 16-channel silicon probes. Detection thresholds, spread of excitation, vector strength, sustained response percentage, and temporal response properties were quantified. Analog stimulation consistently evoked significantly lower activation thresholds than pulsatile stimulation while maintaining comparable or sometimes narrower spatial selectivity across stimulation modes. In contrast, analog stimulation generated lower vector strength, larger tonic response components, and a pronounced level-dependent polarity effect. At low stimulus levels, responses were dominated by the cathodic phase of the sinusoidal waveform, whereas increasing stimulus level responses were elicited by both phases, producing synchronization at twice the stimulus frequency. These findings demonstrate that stimulation waveform strongly influences temporal coding while having relatively little effect on the spatial distribution of neural activation. These results provide a physiological basis for reexamining analog stimulation as an alternative strategy for cochlear implant sound coding.

neuroscience↗

bioRxiv2024

Unveiling the influence of tumor and immune signatures on immune checkpoint therapy in advanced lung cancer

This study investigates the variability among patients with non-small cell lung cancer (NSCLC) in their responses to immune checkpoint inhibitors (ICI). Recognizing that patients with advanced-stage NSCLC rarely qualify for surgical interventions, it becomes crucial to identify biomarkers that influence responses to ICI therapy. We conducted an analysis of single-cell transcriptomes from 33 lung cancer biopsy samples, with a particular focus on 14 core samples taken before the initiation of palliative ICI treatment. Our objective was to link tumor and immune cell profiles with patient responses to ICI. We discovered that ICI non-responders exhibited a higher presence of CD4+ regulatory T cells, resident memory T cells, and TH17 cells. This contrasts with the diverse activated CD8+ T cells found in responders. Furthermore, tumor cells in non-responders frequently showed heightened transcriptional activity in the NF-kB and STAT3 pathways, suggesting a potential inherent resistance to ICI therapy. Through the integration of immune cell profiles and tumor molecular signatures, we achieved an discriminative power (AUC) exceeding 95% in identifying patient responses to ICI treatment. These results underscore the crucial importance of the interplay between tumor and immune microenvironment, including within metastatic sites, in affecting the effectiveness of ICIs in NSCLC.

bioinformatics↗

bioRxiv2023

A marine bacterium elicits the type III secretion-dependent nonhost hypersensitive response in a land plant

Active plant immune response involving programmed cell death called the hypersensitive response (HR) is elicited by microbial effectors delivered through the type III secretion system (T3SS). The marine bacterium Hahella chejuensis contains two T3SSs that are similar to those of animal pathogens, but elicited HR-like cell death in the land plant Nicotiana benthamiana, which was mediated by SGT1 and suppressed by AvrPto1. Thus, the land plant is capable of inducing the cell death in response to type III-secreted effectors of the marine bacterium it never have encountered, suggesting that plants may have evolved to cope with a potential threat posed by alien effectors. One-sentence summaryA marine bacterium Hahella chejuensis harboring functional type III secretion systems induced nonhost hypersensitive response in a land plant Nicotiana benthamiana, which was mediated by SGT1 and suppressed by AvrPto1.

plant biology↗

bioRxiv2022

Magnetic Stimulation Allows Focal Activation of the Mouse Cochlea

Cochlear implants (CIs) strive to restore hearing to those with severe to profound hearing loss by artificially stimulating the auditory nerve. While most CI users can understand speech in a quiet environment, hearing that utilizes complex neural coding (e.g., appreciating music) has proved elusive, probably because of the inability of CIs to create narrow regions of spectral activation. Several novel approaches have recently shown promise for improving spatial selectivity, but substantial design differences from conventional CIs will necessitate much additional safety testing before clinical viability is established. Outside the cochlea, magnetic stimulation from small coils (micro-coils) has been shown to confine activation more narrowly than that from conventional micro-electrodes, raising the possibility that coil-based stimulation of the cochlea could improve the spectral resolution of CIs. To explore this, we delivered magnetic stimulation from micro-coils to multiple locations of the cochlea and measured the spread of activation utilizing a multi-electrode array inserted into the inferior colliculus; responses to magnetic stimulation were compared to analogous experiments with conventional micro-electrodes as well as to the responses to auditory monotones. Encouragingly, the extent of activation with micro-coils was [~]60% narrower than that from electric stimulation and largely similar to the spread arising from acoustic stimulation. The dynamic range of coils was more than three times larger than that of electrodes, further supporting a smaller spread of activation. While much additional testing is required, these results support the notion that coil-based CIs can produce a larger number of independent spectral channels and may therefore improve functional performance. Further, because coil-based devices are structurally similar to existing CIs, fewer impediments to clinical translational are likely to arise.

neuroscience↗