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Biology subjects

Cho, S. Y.

Publications and source records attributed to Cho, S. Y..

5 recordsLinked to original sources

Continuous Monitoring of Head Turns: Compliance, Kinematics, and Reliability of Wearable Sensing

Wearable devices offer objective mobility metrics for continuous monitoring but often focus on traditional measures like step count or gait speed. Other quantitative metrics such as head kinematics may provide valuable insights into mobility, balance, and sensory integration, given the heads central role in coordinating vestibular, ocular, and postural control. Yet, basic knowledge about capturing daily living head turns, including participant compliance, algorithms, normative data, and reliability, is not yet established. This study aimed to resolve this knowledge gap by capturing head and trunk movement kinematics over a 7-day period and to establish normative data in healthy adults. Participants (n = 24) wore head-mounted sensors for an average of 16.38 hours per day (SD = 4.43), completing 5,163 (SD = 1,466) head turns daily, with 72% occurring independently of trunk motion. Head turn amplitude (M = 58.18{degrees}, SD = 4.26{degrees}) was comparable to lumbar turns, while peak velocity was higher for head turns (M = 104.49{degrees}/s, SD = 12.08{degrees}/s). By the second day, all head turn metrics achieved excellent reliability (ICC > 0.9), supporting the feasibility of multi-day monitoring. Additionally, we examined the relationship between head motion and other mobility metrics and established recommendations for implementing similar protocols for capturing future studies, including the minimum number of days required for reliable data collection. Findings from this study provide a foundation for future multi-day continuous monitoring of head kinematics in both healthy and clinical populations.

bioengineering↗

Reconstituting spore cortex peptidoglycan biosynthesis reveals a deacetylase that catalyzes transamidation

Some bacteria survive in nutrient-poor environments and resist killing by antimicrobials by forming spores. The cortex layer of the peptidoglycan cell wall that surrounds mature spores contains a unique modification, muramic-{delta}-lactam, that is essential for spore germination and outgrowth. Two proteins, the amidase CwlD and the deacetylase PdaA, are required for muramic-{delta}-lactam synthesis in cells, but their combined ability to generate muramic-{delta}-lactam has not been directly demonstrated. Here we report an in vitro reconstitution of cortex peptidoglycan biosynthesis, and we show that CwlD and PdaA together are sufficient for muramic-{delta}-lactam formation. Our method enables characterization of the individual reaction steps, and we show for the first time that PdaA has transamidase activity, catalyzing both the deacetylation of N-acetylmuramic acid and cyclization of the product to form muramic-{delta}-lactam. This activity is unique among peptidoglycan deacetylases and is notable because it may involve the direct ligation of a carboxylic acid with a primary amine. Our reconstitution products are nearly identical to the cortex peptidoglycan found in spores, and we expect that they will be useful substrates for future studies of enzymes that act on the spore cortex.

biochemistry↗

Biophysical characterization of the ETV6 PNT domain polymerization interfaces

ETV6 is an ETS family transcriptional repressor that self-associates by its PNT domain to facilitate cooperative DNA binding. Chromosomal translocations frequently generate constitutively active oncoproteins with the ETV6 PNT domain fused to the kinase domain of one of many protein tyrosine kinases. Although an attractive target for therapeutic intervention, the propensity of the ETV6 PNT domain to polymerize via the tight head-to-tail association of two relatively flat interfaces makes it challenging to identify suitable small molecule inhibitors of this protein-protein interaction. Herein we provide a comprehensive biophysical characterization of the ETV6 PNT domain interaction interfaces to aid future drug discovery efforts and help define the mechanisms by which its self-association mediates transcriptional repression. Using NMR spectroscopy, X-ray crystallography, and molecular dynamics simulations, we demonstrate that ETV6 PNT domain variants with monomerizing mutations adopt very stable helical bundle folds that do not change in conformation upon self-association. Amide hydrogen exchange and surface plasmon resonance-monitored alanine scanning mutagenesis studies identified hot spot regions within the self-association interfaces. These regions include both central hydrophobic residues and flanking salt-bridging residues. Collectively, these studies indicate that small molecules targeted to these hydrophobic or charged regions within the relatively rigid interfaces could potentially serve as orthosteric inhibitors of ETV6 PNT domain polymerization.

biochemistry↗

ASpediaFI: Functional interaction analysis of alternative splicing events

Alternative splicing (AS) regulates biological process governing phenotype or disease. However, it is challenging to systemically analyze global regulation of AS events, their gene interactions, and functions. Here, we introduce a novel application, ASpediaFI for identifying AS events and co-regulated gene interactions implicated in pathways. Our method establishes an interaction network including AS events, performs random walk with restart, and finally identifies a functional subnetwork containing the AS event. We validated the capability of ASpediaFI to interpret biological relevance based on three case studies. Using simulation data, we achieved higher accuracy than with other methods and detected pathway-associated AS events.

bioinformatics↗

A role for KIF9 in male fertility

A mouse was generated containing a floxed exon 3 of the gene for the kinesin family member KIF9. By in situ hybridization, expression of KIF9 mRNA was highest in the testis and was also strong in epithelia containing multi-ciliated cells such as the ependyma, bronchioles and oviduct. Deletion of the exon led to loss of KIF9 expression at the mRNA and protein level with no effect on viability. However, homozygous KIF9 knockout males were sterile. Although KIF9 knockout sperm were motile, they were unable to fertilize oocytes in an in vitro fertilization assay. Closer examination of sperm motility indicated a subtle difference in waveform. Our results suggest that KIF9 plays a role male fertility, possibly through regulation of flagellar waveforms in ciliated cells.

developmental biology↗