Biology subjects

Li, Y. C.

Publications and source records attributed to Li, Y. C..

7 recordsLinked to original sources

bioRxiv2025

The contribution of vestibular and proprioceptive signals to trunk stabilization varies between postural tasks and between walking speeds.

Stabilizing the upright posture of the trunk relies on vestibular and proprioceptive afference. Previous studies found that the feedback responses to sensory afference vary between postures and tasks. We investigated whether and how vestibular and proprioceptive afference contribute to trunk stabilization during different postural tasks, and during walking at different speeds. Twelve healthy adults performed tasks in a random order: sitting, standing on the right foot or both feet, and treadmill walking at five speeds: 0.8, 2.0, 3.2, 4.3 and 5.5 km/h, while exposed to unilateral muscle vibration on the right paraspinal muscles at the level of the second lumbar vertebra, or to a step-like electrical vestibular stimulation (EVS) with the anode behind the left ear. The mediolateral displacements of markers at the sixth thoracic level and sacrum in the global coordinate system were used to evaluate the responses to sensory stimulation. No significant responses to EVS at T6 and sacrum level were found in sitting and standing. Responses to muscle vibration were significant and differed between unipedal standing compared to sitting and bipedal standing. The latter suggests a different interpretation of the sensation of muscle lengthening in these postures. During walking, the magnitude of the responses to both stimuli increased from very slow speeds to moderate speeds. From moderate to higher speeds, responses to muscle vibration decreased, whereas responses to EVS plateaued. These findings suggest speed-dependent modulation of vestibular and proprioceptive contributions in trunk stabilization during walking. Summary statementBy applying electrical vestibular stimulation and muscle vibration, we found that how vestibular and proprioceptive signals are used for trunk stabilization differs between postural tasks and walking speeds.

neuroscience↗

bioRxiv2024

The effect of head orientation on vestibular signal-based modulation of paraspinal muscle activity during walking

Vestibulospinal reflexes play a role in maintaining the upright posture of the trunk. Head orientation has been shown to modify the vestibulospinal reflexes during standing. This study investigated how vestibular signals affect paraspinal muscle activity during walking, and whether head orientation changes these effects. Sixteen participants were instructed to walk on a treadmill for 8 min at 78 steps/min and 2.8 km/h in four conditions defined by the presence of electrical vestibular stimulation (EVS) and by head orientation (facing forward and facing leftward), while bipolar electromyography (EMG) was recorded bilaterally from the paraspinal muscles from cervical to lumbar levels. In both head orientations, significant phasic EVS-EMG coherence (p < 0.01) in the paraspinal muscles was observed at ipsilateral and/or contralateral heel strikes. Compared to walking with the head forward, a significant decrease (p < 0.05) was found in EVS evoked responses (i.e., EVS-EMG coherence and gain) when participants walked with the leftward head orientation, with which EVS induced disturbance in the sagittal plane. This overall decrease may be explained by less need of feedback control for walking stabilization in the sagittal plane compared to in the frontal plane. The decrease in coherence was only significant at the left lower vertebral levels and at the right upper vertebral levels around left heel strikes (p < 0.05). Together, these findings confirm the contribution of the vestibular afferent signals to the control of paraspinal muscle activity during walking and indicate that this control is changed in response to different head orientations. Key Point SummaryO_LIVestibulospinal reflexes simultaneously contribute to stabilizing the centre of mass trajectory and to maintaining an upright posture of the trunk. C_LIO_LIHead orientation, which challenges stability via altered visual, vestibular and proprioceptive signals, modifies vestibulospinal reflexes during standing. C_LIO_LITo explore the impact of head orientation during walking, we recorded bilateral surface EMG of cervical to lumbar paraspinal muscles, and characterized coherence, gain and delay between EMG and electrical vestibular stimulation, during walking with head facing forward and leftward. C_LIO_LIWhen walking with head facing leftward, vestibular stimulation caused disturbance in sagittal plane. Phasic response in paraspinal muscles with a significant smaller magnitude was found compared to facing forward. C_LIO_LIOur results agree with the idea that less feedback control is required for walking stabilization in the sagittal plane and confirm that vestibular afference modulates paraspinal muscle activity for trunk control during walking, and this modulation is changed in response to head orientation. C_LI

physiology↗

bioRxiv2023

KinAce: a web portal for exploring kinase-substrate interactions

Interactions between protein kinases and their substrates are critical for the modulation of complex signaling pathways. Currently, there is a large amount of information available about kinases and their substrates in disparate public databases. However, these data are difficult to interpret in the context of cellular systems, which can be facilitated by examining interactions among multiple proteins at once, such as the network of interactions that constitute a signaling pathway. We present KinAce, a user-friendly web portal that integrates and shares information about kinase-substrate interactions from multiple databases of post-translational modifications. KinAce enables the visual exploration of these interactions in systems contexts, such as pathways, domain families, and custom protein set inputs, in an interactive fashion. We expect KinAce to be useful as a knowledge discovery tool for kinase-substrate interactions, and the aggregated KinAce dataset to be useful for protein kinase studies and systems-level analyses. The portal is available at https://kinace.kinametrix.com/.

systems biology↗

bioRxiv2023

Vertebral level specific modulation of paraspinal muscle activity based on vestibular signals during walking.

Evoking muscle responses by electrical vestibular stimulation (EVS) may help to understand the contribution of the vestibular system to postural control. Although paraspinal muscles play a role in postural stability, the vestibulo-muscular coupling of these muscles during walking has rarely been studied. This study aimed to investigate how vestibular signals affect paraspinal muscle activity at different vertebral levels during walking with preferred and narrow step width. Sixteen healthy participants were recruited. Participants walked on a treadmill for 8 minutes at 78 steps/min and 2.8 km/h, at two different step width, either with or without EVS. Bipolar electromyography was recorded bilaterally from the paraspinal muscles at eight vertebral levels from cervical to lumbar. Coherence, gain, and delay of EVS and EMG responses were determined. Significant EVS-EMG coupling (p<0.01) was found at ipsilateral and/or contralateral heel strikes. This coupling was mirrored between left and right relative to the midline of the trunk and between the higher and lower vertebral levels, i.e., a peak occurred at ipsilateral heel strike at lower levels, whereas it occurred at contralateral heel strike at higher levels. EVS-EMG coupling only partially coincided with peak muscle activity. EVS-EMG coherence slightly, but not significantly, increased when walking with narrow steps. No significant differences were found in gain and phase between the vertebral levels or step width conditions. In summary, vertebral level specific modulation of paraspinal muscle activity based on vestibular signals might allow a fast, synchronized, and spatially co-ordinated response along the trunk during walking. Key Points SummaryO_LIMediolateral stabilization of gait requires an estimate of the state of the body, which is affected by vestibular afference. C_LIO_LIDuring gait, the heavy trunk segment is controlled by phasic paraspinal muscle activity and in rodents the medial and lateral vestibulospinal tracts activate these muscles. C_LIO_LITo gain insight in vestibulospinal connections in humans and their role in gait, we recorded paraspinal surface EMG of cervical to lumbar paraspinal muscles, and characterized coherence, gain and delay between EMG and electrical vestibular stimulation, during slow walking. C_LIO_LIVestibular stimulation caused phasic, vertebral level specific modulation of paraspinal muscle activity at delays of around 40 milliseconds, which was mirrored between left, lower and right, upper vertebral levels. C_LIO_LIOur results indicate that vestibular afference causes fast, synchronized, and spatially co-ordinated responses of the paraspinal muscles along the trunk, that simultaneously contribute to stabilizing the centre of mass trajectory and to keeping the head upright. C_LI

physiology↗

bioRxiv2023

Exploring the Druggable Conformational Space of Protein Kinases Using AI-Generated Structures

Protein kinase function and interactions with drugs are controlled in part by the movement of the DFG and [a]C-Helix motifs, which enable kinases to adopt various conformational states. Small molecule ligands elicit therapeutic effects with distinct selectivity profiles and residence times that often depend on the kinase conformation(s) they bind. However, the limited availability of experimentally determined structural data for kinases in inactive states restricts drug discovery efforts for this major protein family. Modern AI-based structural modeling methods hold potential for exploring the previously experimentally uncharted druggable conformational space for kinases. Here, we first evaluated the currently explored conformational space of kinases in the PDB and models generated by AlphaFold2 (AF2) (1) and ESMFold (2), two prominent AI-based structure prediction methods. We then investigated AF2s ability to predict kinase structures in different conformations at various multiple sequence alignment (MSA) depths, based on this parameters ability to explore conformational diversity. Our results showed a bias within the PDB and predicted structural models generated by AF2 and ESMFold toward structures of kinases in the active state over alternative conformations, particularly those conformations controlled by the DFG motif. Finally, we demonstrate that predicting kinase structures using AF2 at lower MSA depths allows the exploration of the space of these alternative conformations, including identifying previously unobserved conformations for 398 kinases. The results of our analysis of structural modeling by AF2 create a new avenue for the pursuit of new therapeutic agents against a notoriously difficult-to-target family of proteins. Significance StatementGreater abundance of kinase structural data in inactive conformations, currently lacking in structural databases, would improve our understanding of how protein kinases function and expand drug discovery and development for this family of therapeutic targets. Modern approaches utilizing artificial intelligence and machine learning have potential for efficiently capturing novel protein conformations. We provide evidence for a bias within AlphaFold2 and ESMFold to predict structures of kinases in their active states, similar to their overrepresentation in the PDB. We show that lowering the AlphaFold2 algorithms multiple sequence alignment depth can help explore kinase conformational space more broadly. It can also enable the prediction of hundreds of kinase structures in novel conformations, many of whose models are likely viable for drug discovery.

bioinformatics↗

bioRxiv2021

Verification of SARS-CoV-2-Encoded small RNAs and contribution to Infection-Associated lung inflammation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. SARS-CoV-2 is a positive-stranded RNA virus belongs to Coronaviridae family. The viral genome of SARS-CoV-2 contains around 29.8 kilobase with a 5'-cap structure and 3'-poly-A tail, and shows 79.2% nucleotide identity with human SARS-CoV-1, which caused the 2002-2004 SARS outbreak. As the successor to SARS-CoV-1, SARS-CoV-2 now has circulated across the globe. There is a growing understanding of SARS-CoV-2 in virology, epidemiology, and clinical management strategies. In this study, we verified the existence of two 18-22 nt small viral RNAs (svRNAs) derived from the same precursor in human specimens infected with SARS-CoV-2, including nasopharyngeal swabs and formalin-fixed paraffin-embedded (FFPE) explanted lungs from lung transplantation of COVID-19 patients. We then simulated and confirmed the formation of these two SARS-CoV-2-Encoded small RNAs in human lung epithelial cells. And the potential pro-inflammatory effects of the splicing and maturation process of these two svRNAs in human lung epithelial cells were also explored. By screening cytokine storm genes and the characteristic expression profiling of COVID-19 in the explanted lung tissues and the svRNAs precursor transfected human lung epithelial cells, we found that the maturation of these two small viral RNAs contributed significantly to the infection associated lung inflammation, mainly via the activation of the CXCL8, CXCL11 and type I interferon signaling pathway. Taken together, we discovered two SARS-CoV-2-Encoded small RNAs and investigated the pro-inflammatory effects during their maturation in human lung epithelial cells, which might provide new insight into the pathogenesis and possible treatment options for COVID-19.

microbiology↗

bioRxiv2020

Hyaluronic Acid on the Urokinase Sustained Release with a Hydrogel System Composed of Poloxamer 407: Enhanced Stability of Intracellular Interaction by Adding HA.

Pleural empyema is an inflammatory condition characterized by accumulation of pus inside the pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause proliferation of fibroblasts and deposition of extracellular matrix, which lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through a chest drainage tube is frequently used for fibrinolysis in patients with empyema. However, urokinase treatment requires multiple instillation (2-3 times per day, for 4-8 days) and easily flows out from the chest drainage tube due to its high water solubility. In this in vitro study, we developed a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) for optimal loading and release of urokinase. Our results show that the addition of HA to poloxamer gels provides a significantly more compact microstructure, with smaller pore sizes (**p < 0.001). The differential scanning calorimetry (DSC) profile revealed no influence on the micellization intensity of poloxamer gel by HA. The 25% poloxamer-based gel was significantly superior to the 23% poloxamer-based gel, with slower gel erosion when comparing the 16th hour residual gel weight of both gels (*p < 0.05; **p < 0.001). The 25% poloxamer-HA gel also exhibited a superior urokinase release profile and longer release time. A Fourier-transform infrared spectroscopy (FT-IR) study of the P407/HA hydrogel showed no chemical interactions between P407 and HA in the hydrogel system. The thermoresponsive P407/HA hydrogel may have a promising potential in the loading and delivery of hydrophilic drugs. On top of that, in vitro toxicity test of this combination demonstrates a lower toxicity.

pharmacology and toxicology↗