Biology subjects

Cheng, Y.-S.

Publications and source records attributed to Cheng, Y.-S..

4 recordsLinked to original sources

bioRxiv2025

Distinct cortical encoding of acoustic and electrical cochlear stimulation

Cochlear implants are neuroprosthetic devices that restore hearing and speech comprehension to profoundly deaf humans and represent an exemplar application of biomedical engineering and research to clinical conditions. However, the utility of these devices in many subjects is limited, largely due to lack of information about how neural circuits respond to implant stimulation. Recently we showed that deafened rats can use cochlear implants to recognize sounds, and that this training refined the responses of single neurons in the primary auditory cortex. Here we asked how local populations of cortical neurons represent acute implant stimuli, using electrode arrays we developed for cortical surface recordings for micro-electrocorticography ({micro}ECoG), a form of intracranial electroencephalography (iEEG). We found that there was a coarse, non-random spatial organization with limited evidence for consistent, sharply graded cochleotopy across recording sites, relative to a clearer tonotopic spatial representation in normal-hearing rats. Single-trial iEEG responses to acoustic inputs were more reliable than responses to cochlear implant stimulation, although stimulus identity could be successfully decoded in both cases. However, the spatio-temporal response profiles to acoustic vs cochlear implant stimulation were substantially different. Decoders trained on acoustic responses showed essentially zero information transfer when tested on electrical stimulation responses in the same animals after deafening and cochlear implant stimulation. Thus, while acute cochlear implant stimulation evoked spatially non-random cortical activity with coarse cochleotopic structure, the dynamics of network activity were substantially different from those evoked by acoustic stimulation, with possible implications for perceptual similarity that remain to be tested.

neuroscience↗

bioRxiv2025

INVESTIGATING THE INHIBITORY EFFECTS OF BLEBBISTATIN ON ACTOMYOSIN INTERACTIONS IN MYOFIBRILS AND ISOLATED MYOFILAMENTS

Myosin II is the molecular motor responsible for muscle contraction. Myosin II hydrolyses ATP into Pi and ADP, to convert chemical energy into mechanical work while attached to actin filaments. The relation between force generation and Pi release remains unclear. Many studies use chemical substances, such as blebbistatin, to study the transitions during actomyosin interactions. Blebbistatin and its derivatives selectively inhibit the actin-activated ATPase of myosin II, accumulating myosin cross-bridges in a pre-power-stroke state. Although the effects of blebbistatin have been explored, it is still unclear how blebbistatin affects force generation and the velocity of contraction. In this study, we used individual myofibrils, myosin and actin filaments, and isolated heavy meromyosin (HMM) and actin filaments to characterize the effects of blebbistatin. We observed that increasing concentrations of blebbistatin (i) decreased the force produced by myofibrils and isolated myosin filaments, (ii) decreased the maximum velocity of shortening produced by myofibrils and the myosin-induced actin sliding velocity, (iii) decreased the curvature of the force-velocity relation in a dose-dependent manner. Furthermore, UV radiation reduced the effect of blebbistatin, which was partially reversed if blebbistatin was bound to myosin before exposure to UV light. These results show that blebbistatin alters force and velocity generation at the molecular, myofilamentous and myofibrillar levels. This study has interesting implications in fields which rely on using blebbistatin to study cellular processes and confirms several results published in different experimental arrangements. Thus, this study is exploratory and confirmatory, and the findings have utility surrounding cell migration, muscle biophysics, cellular reproduction, or any processes that rely on the action of myosin II.

biophysics↗

bioRxiv2024

Oxidation-induced structural changes in actin and myosin evaluated by computational simulation, machine learning modeling and high-speed AFM

High levels of reactive oxygen species produced during muscle oxidative stress are implicated in the development of several muscle diseases. To better understand the mechanism behind a reduced myosin force generation under oxidizing conditions, we analyzed the structural and functional changes in the actin and actin-myosin complex using high-speed atomic force microscopy (HS-AFM), simulated HS-AFM, and molecular dynamics (MD) simulation. Computational oxidative nitration of tyrosine residues demonstrated instability in the molecular structure of the F-actin subunit. Cross-section analysis of the simulated HS-AFM images revealed a shift in the height values ([~]0.2-1.5 nm in magnitude) between the non-oxidized and oxidized actin, which correspond to the height differences observed in HS-AFM experiments with in vitro oxidized F-actin. The oxidation-induced structural alterations in actin impact myosin molecule displacement on the single-molecule level. The displacements of myosin heads along the F-actin filaments in the presence of ATP involve the binding of the myosin molecule to a specific site on the F-actin filament, followed by the rotation of the myosin lever arm, which triggers the release of inorganic phosphate (Pi). Subsequently, the myosin head detaches from the F-actin and re-binds to a new site on the filament. The formation of the SIN-1-treated F-actin-myosin complex in the presence of ATP resulted in a change in myosin head displacement size, with a significant decrease in the frequency of long displacements ([≥] 4 nm). These results suggest that oxidation decreases the pool of the weak-bound myosin molecules and shortens the long displacements related to the Pi release step, reducing the force generation by myosin motors.

biophysics↗

bioRxiv2018

Structural insights into DNA sequence recognition by Arabidopsis ETHYLENE RESPONSE FACTOR 96

The phytohormone ethylene is widely involved in many developmental processes and is a crucial regulator of defense responses against biotic and abiotic stresses in plants. Ethylene-responsive element binding protein (EREBP), a member of the APETALA2/ethylene response factor (AP2/ERF) superfamily, is a transcription factor that regulates stress-responsive genes by recognizing a specific cis-acting element of target DNA. A previous study showed only the NMR structure of the AP2/ERF domain of AtERF100 in complex with a GCC box DNA motif. In this report, we determined the crystal structure of AtERF96 in complex with a GCC box at atomic resolution. We analyzed the binding residues of the conserved AP2/ERF domain in the DNA recognition sequence. In addition to the AP2/ERF domain, an N-terminal -helix of AtERF96 participates in DNA interaction in the flanking region. We also demonstrated the structure of AtERF96 EDLL motif, a unique conserved motif in the group IX of AP2/ERF family, is critical for the transactivation of defense-related genes. Our study establishes the structural basis of the AtERF96 transcription factor in complex with the GCC box, as well as the DNA binding mechanisms of the N-terminal -helix and AP2/ERF domain.

plant biology↗