Biology subjects

Lee, Y.-C.

Publications and source records attributed to Lee, Y.-C..

4 recordsLinked to original sources

bioRxiv2020

De Novo Discovery of High Affinity Peptide Binders for the SARS-CoV-2 Spike Protein

The {beta}-coronavirus SARS-CoV-2 has caused a global pandemic. Affinity reagents targeting the SARS-CoV-2 spike protein, the most exposed surface structure of the virus, are of interest for the development of therapeutics and diagnostics. We used affinity selection-mass spectrometry for the rapid discovery of synthetic high affinity peptide binders for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. From library screening with 800 million synthetic peptides, we identified three sequences with nanomolar affinities (dissociation constants Kd = 80 to 970 nM) for RBD and selectivity over human serum proteins. Picomolar RBD concentrations in biological matrix could be detected using the biotinylated lead peptide in ELISA format. These peptides might associate with the SARS-CoV-2-spike-RBD at a site unrelated to ACE2 binding, making them potential orthogonal reagents for sandwich immunoassays. We envision our discovery as a robust starting point for the development of SARS-CoV-2 diagnostics or conjugates for virus directed delivery of therapeutics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/317131v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@803e9borg.highwire.dtl.DTLVardef@18e5d74org.highwire.dtl.DTLVardef@1998310org.highwire.dtl.DTLVardef@16ba5cc_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

COPB2 haploinsufficiency causes a coatopathy with osteoporosis and developmental delay

Coatomer complexes function in the sorting and trafficking of proteins between subcellular organelles. Pathogenic variants in coatomer subunits or associated factors have been reported in multi-systemic disorders, i.e., coatopathies, that can affect the skeletal and central nervous systems. We have identified loss-of-function variants in COPB2, a component of the coatomer complex I (COPI), in individuals presenting with osteoporosis, fractures and developmental delay of variable severity. Because the role of COPB2 in bone has not been characterized, we studied the effect of COPB2 deficiency on skeletal development in mice and zebrafish. Copb2+/- mice showed low bone mass and decreased bone strength. In zebrafish, larvae carrying a copb2 heterozygous frameshift variant showed delayed mineralization. copb2-null embryos showed endoplasmic reticulum (ER) and Golgi disorganization, and embryonic lethality. COPB2 siRNA-treated fibroblasts showed delayed collagen trafficking with retention of type I collagen in the ER and Golgi, and altered distribution of Golgi markers. Our data suggest that COPB2 haploinsufficiency leads to disruption of intracellular collagen trafficking and osteoporosis, which may improve with ascorbic acid supplementation. This work highlights the role of COPI complex as a critical regulator of bone mass and identifies a new form of coatopathy due to COPB2 deficiency.

genetics↗

bioRxiv2020

Segmentation boosting with compensation methods in optical coherence tomography angiography images

Optical coherence tomography angiography is a noninvasive imaging modality to establish the diagnosis of retinal vascular diseases. However, angiography images are significantly interfered if patients jitter or blink. In this study, a novel retinal image analysis method to accurately detect blood vessels and compensate the effect of interference was proposed. We call this the patch U-Net compensation (PUC) system, which is based on the famous U-Net. Several techniques, including a better training mechanism, direction criteria, area criteria, gap criteria, and probability map criteria, have been proposed to improve its accuracy. Simulations show that the proposed PUC achieves much better performance than state-of-art methods.

bioengineering↗

bioRxiv2020

Impact of urolithiasis and hydronephrosis on acute kidney injury in patients with urinary tract infection

BackgroundUrolithiasis is a common cause of urinary tract obstruction and urinary tract infection (UTI). This study aimed to identify whether urolithiasis with or without hydronephrosis has an impact on acute kidney injury (AKI) in patients with UTI. Methods and findingsThis retrospective study enrolled hospitalized UTI patients who underwent imaging in an acute care setting from January 2006 to April 2019. Of the 1113 participants enrolled, 191 (17.2%) had urolithiasis and 76 (6.8%) had ureteral stone complicated with hydronephrosis. Multivariate logistic regression analysis showed that in UTI patients with urolithiasis, the presence of ureteral stone with concomitant hydronephrosis was an independent risk factor for AKI (odds ratio [OR] 2.345, 95% confidence interval [CI] 1.128-4.876, P = 0.023). In addition, urolithiasis was associated with an increased risk for AKI (OR 2.484, 95% CI 1.398-4.415, P = 0.002) in UTI patients without hydronephrosis. ConclusionThe presence of ureteral stone with hydronephrosis increases the risk for AKI of UTI patients with urolithiasis, and urolithiasis remains a risk factor of AKI in UTI patients without hydronephrosis.

pathology↗