Biology subjects

Werth, J. C.

Publications and source records attributed to Werth, J. C..

3 recordsLinked to original sources

bioRxiv2026

Predicting neutron radiation exposure characteristics from an in vitro human skin model using RNA-seq

Accurate assessment of low-dose neutron radiation exposure remains a central challenge in biodosimetry, particularly for applications requiring non-invasive sample types such as skin. Here, we characterized the transcriptional response of a three-dimensional in vitro human skin model (EpiDermFT) to neutron irradiation at doses up to 0.75 Gy, measured from pre-exposure through a 14-day post-exposure period. RNA sequencing revealed greater than 800 significantly altered genes, including upregulation of FOS, FOSB, CDKN1A, MDM2, and GADD45A, and downregulation of NRG1, H3C11, and CENPX. Gene ontology enrichment indicated activation of DNA damage checkpoint signaling, cell cycle arrest, and stress-response pathways, alongside suppression of nucleosome assembly and DNA replication processes. Machine learning models trained on transcriptomic features exhibited strong predictive performance across biodosimetric endpoints. Classification models accurately distinguished irradiated from sham samples (AUC > 0.99), and regression models achieved high accuracy for estimating both absorbed dose (R2 = 0.97) and days post-exposure (R2 = 0.99). The latter, while highly predictive, may partially reflect transcriptional shifts associated with progressive degradation of the in vitro tissue model over time. Collectively, these findings demonstrate that RNA-based molecular signatures from human skin tissue provide a robust framework for quantitative estimation of neutron radiation exposure and temporal response dynamics.

genomics↗

bioRxiv2022

Dynamics of spike time encoding in the olfactory bulb

In the mammalian olfactory bulb (OB), gamma oscillations in the local field potential are generated endogenously during odor sampling. Such oscillations arise from dynamical systems that generate organized periodic behavior in neural circuits, and correspond to spike timing constraints at fine timescales. While the cellular and network mechanisms of gamma oscillogenesis in the OB are reasonably well established, it remains unclear how these fine-timescale dynamics serve to represent odors. Are patterns of spike synchrony on the gamma timescale replicable and odor-specific? Does the transformation to a spike-timing metric embed additional computations? To address these questions, we used OB slices to examine the spike timing dynamics evoked by "fictive odorants" generated via spatiotemporally patterned optogenetic stimulation of olfactory sensory neuron axonal arbors. We found that a small proportion of mitral/tufted cells phase-lock strongly to the fast oscillations evoked by fictive odorants, and exhibit tightly coupled spike-spike synchrony on the gamma timescale during this stimulation. Moreover, the specific population of synchronized neurons differed based on the "quality", but not the "concentration", of the fictive odorant presented, and was conserved across multiple presentations of the same fictive odorant. Given the established selectivity of piriform cortical pyramidal neurons for inputs synchronized on this timescale, we conclude that spike synchronization on a milliseconds timescale is a metric by which the OB encodes and exports afferent odor information in a concentration-invariant manner. As a corollary, mitral/tufted cell spikes that are not organized in time may not contribute effectively to the ensemble odor representation.

neuroscience↗

bioRxiv2021

Myosin-driven Nucleation of Actin Filaments Drives Stereocilia Development Critical for Hearing

The assembly and maintenance of actin-based mechanosensitive stereocilia in the cochlea is critical for lifelong hearing. Myosin-15 (MYO15) is hypothesized to modulate stereocilia height by trafficking actin regulatory proteins to their tip compartments, where actin polymerization must be precisely controlled during development. We identified a mutation (p.D1647G) in the MYO15 motor-domain that initially maintained trafficking, but caused progressive hearing loss by stunting stereocilia growth, revealing an additional function for MYO15. Consistent with its maintenance of tip trafficking in vivo, purified p.D1647G MYO15 modestly reduced actin-stimulated ATPase activity in vitro. Using ensemble and single-filament fluorescence in vitro assays, we demonstrated that wild-type MYO15 directly accelerated actin filament polymerization by driving nucleation, whilst p.D1647G MYO15 blocked this activity. Collectively, our studies suggest direct actin nucleation by MYO15 at the stereocilia tip is necessary for elongation in vivo, and that this is a primary mechanism disrupted in DFNB3 hereditary human hearing loss.

cell biology↗