Biology subjects

Kim, A. B.

Publications and source records attributed to Kim, A. B..

3 recordsLinked to original sources

bioRxiv2026

Daylight, Daily Rhythms, and Downstream Physiology: A Translational Study in Diurnal Nile Grass Rats (Arvicanthis niloticus)

The circadian system evolved under natural light-dark cycles, while modern humans spend much of their time indoors under electric lighting that differs substantially from daylight in intensity, spectral composition, and temporal structure. How such lighting environments influence circadian system has not been systematically examined in a diurnal animal model under ecologically relevant conditions. In this study, we used the diurnal Nile grass rat (Arvicanthis niloticus) to assess daily locomotor rhythms across four lighting conditions designed to approximate common human exposure scenarios: rectangular daylight (D65-R; [~]5,600 lux), semi-sigmoidal daylight mimicking natural intensity dynamics (D65-S; matched peak intensity with [~]50% lower cumulative energy), fluorescent indoor light (F12; [~]150 lux), and fluorescent light supplemented with a one-hour midday daylight pulse (F12+D65-P). Using a within-subject design (n = 8), male grass rats were housed under each condition for two weeks. D65-R produced the highest daytime activity levels and the strongest day/night activity ratio, consistent with robust circadian entrainment. Despite matching peak intensity, D65-S did not yield comparable circadian outcomes, indicating that cumulative photon exposure, rather than peak intensity alone, contributes to entrainment strength. Notably, the addition of a one-hour midday daylight pulse (D65-P) partially increased circadian amplitude under otherwise fluorescent conditions, with higher periodogram amplitude relative to F12 alone. A separate cohort of males was exposed to D65-R or F12 for six weeks (n = 10/condition) to assess physiological outcomes, including metabolic and reproductive measures. Compared with the D65-R group, F12 group showed higher diabetic rate (10% vs. 40%) and reduced sperm mobility (45{+/-}6 vs. 19{+/-}1 %), consistent with potential downstream correlates of circadian rhythm disruption. Together, these findings demonstrate that lighting conditions characteristic of indoor environments produce weaker circadian organization than daylight-equivalent lighting in a diurnal rodent, which underscore the importance of light quality in shaping circadian rhythms and downstream physiological processes.

animal behavior and cognition↗

bioRxiv2025

Preconditioning Matters: Enhancing or Impairing Antitumor Immunity with DC Vaccines

Preconditioning regimens are essential for the success of adoptive cell therapies like CAR T-cells due to effects on the T-cell response, yet they are underexplored and generally absent from cancer vaccine clinical trials. To address this gap, we evaluated the impact of various preconditioning strategies on dendritic cell (DC) vaccine efficacy in a murine tumor model. Mice bearing syngeneic KP tumors expressing ovalbumin received preconditioning with low-dose radiation (LD RT; whole body or tumor only), cyclophosphamide, paclitaxel, LD RT plus cyclophosphamide, or no preconditioning, followed by administration of antigen-loaded DC1s. Tumor growth, survival, and antigen-specific CD8+ T-cell responses were assessed. LD RT preconditioning, whether whole body or tumor-directed, significantly enhanced vaccine-induced antitumor CD8+ T-cell responses and improved survival compared to DC vaccine alone and all other groups. Cyclophosphamide preconditioning reduced vaccine efficacy and negated the benefits of LD RT, while paclitaxel had no significant effect. Notably, whole-body LD RT induced the strongest antigen-specific T-cell response. These findings demonstrate that, similar to CAR T-cell therapy, preconditioning regimens can significantly influence cancer vaccine outcomes. Rational selection of preconditioning agents may either maximize or minimize the therapeutic potential of DC cancer vaccines, and should be considered carefully in clinical trials.

immunology↗

bioRxiv2023

Chimeric Antigen Receptor Macrophages Target and Resorb Amyloid Plaques in a Mouse Model of Alzheimer's Disease

Substantial evidence suggests a role for immunotherapy in treating Alzheimers disease (AD). Several monoclonal antibodies targeting aggregated forms of beta amyloid (A{beta}), have been shown to reduce amyloid plaques and in some cases, mitigate cognitive decline in early-stage AD patients. We sought to determine if genetically engineered macrophages could improve the targeting and degradation of amyloid plaques. Chimeric antigen receptor macrophages (CAR-Ms), which show promise as a cancer treatment, are an appealing strategy to enhance target recognition and phagocytosis of amyloid plaques in AD. We genetically engineered macrophages to express a CAR containing the anti-amyloid antibody aducanumab as the external domain and the Fc receptor signaling domain internally. CAR-Ms recognize and degrade A{beta} in vitro and on APP/PS1 brain slices ex vivo; however, when injected intrahippocampally, these first-generation CAR-Ms have limited persistence and fail to reduce plaque load. We overcame this limitation by creating CAR-Ms that secrete M-CSF and self-maintain without exogenous cytokines. These CAR-Ms have greater survival in the brain niche, and significantly reduce plaque load locally in vivo. These proof-of-principle studies demonstrate that CAR-Ms, previously only applied to cancer, may be utilized to target and degrade unwanted materials, such as amyloid plaques in the brains of AD mice. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/538637v2_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@561cd6org.highwire.dtl.DTLVardef@17f362forg.highwire.dtl.DTLVardef@be83ecorg.highwire.dtl.DTLVardef@1c735ce_HPS_FORMAT_FIGEXP M_FIG Amyloid targeting CAR Macrophages engineered to secrete M-CSF promote their own local survival and expansion while resorbing amyloid plaques in the brains of Alzheimers disease APP/PS1 mice, resulting in significant local clearance of amyloid plaques of all sizes. C_FIG

immunology↗