Biology subjects

Oh, Y. J.

Publications and source records attributed to Oh, Y. J..

4 recordsLinked to original sources

bioRxiv2024

Dependence of Contextual Modulation in Macaque V1 on Interlaminar Signal Flow

In visual cortex, neural correlates of subjective perception can be generated by modulation of activity from beyond the classical receptive field (CRF). In macaque V1, activity generated by nonclassical receptive field (nCRF) stimulation involves different intracortical circuitry than activity generated by CRF stimulation, suggesting that interactions between neurons across V1 layers differ under CRF and nCRF stimulus conditions. Using Neuropixels probes, we measured border ownership modulation within large, local populations of V1 neurons. We found that neurons in single columns preferred the same side of objects located outside of the CRF. In addition, we found that cross-correlations between pairs of neurons situated across feedback/horizontal and input layers differed between CRF and nCRF stimulation. Furthermore, independent of the comparison with CRF stimulation, we observed that the magnitude of border ownership modulation increased with the proportion of information flow from feedback/horizontal layers to input layers. These results demonstrate that the flow of signals between layers covaries with the degree to which neurons integrate information from beyond the CRF.

neuroscience↗

bioRxiv2021

Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans

Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we show that a "lectibody" consisting of the high-mannose glycan-binding lectin Avaren and human IgG1 Fc (AvFc) selectively recognizes a range of cell lines derived from lung, breast, colon and blood cancers at nanomolar concentrations. AvFcs binding to the non-small cell lung cancer (NSCLC) cell lines A549 and H460 was characterized in detail. Co-immunoprecipitation proteomics analysis revealed that epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) are among the lectibodys common targets in these cells. AvFc blocked the activation of EGFR and IGF1R by their respective ligands in A549 cells and inhibited the migration of A549 and H460 cells upon stimulation with EGF and IGF1. Furthermore, AvFc induced potent Fc-mediated cytotoxic effects and significantly retarded A549 and H460 tumor growth in SCID mice. Immunohistochemistry analysis of primary lung tissues from NSCLC patients demonstrated that AvFc preferentially binds to tumors over adjacent non-tumor tissues. Our findings provide evidence that increased abundance of high-mannose glycans in the glycocalyx of cancer cells can be a druggable target, and AvFc may provide a new tool to probe and target this tumor-associated glycobiomarker.

cancer biology↗

bioRxiv2021

Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites

New SARS-CoV-2 variants are continuously emerging with critical implications for therapies or vaccinations. All 22 N-glycan sites of SARS-CoV-2 Spike remain highly conserved among the variants B.1.1.7, 501Y.V2 and P.1, opening an avenue for robust therapeutic intervention. Here we used a comprehensive library of mammalian carbohydrate-binding proteins (lectins) to probe critical sugar residues on the full-length trimeric Spike and the receptor binding domain (RBD) of SARS-CoV-2. Two lectins, Clec4g and CD209c, were identified to strongly bind to Spike. Clec4g and CD209c binding to Spike was dissected and visualized in real time and at single molecule resolution using atomic force microscopy. 3D modelling showed that both lectins can bind to a glycan within the RBD-ACE2 interface and thus interferes with Spike binding to cell surfaces. Importantly, Clec4g and CD209c significantly reduced SARS-CoV-2 infections. These data report the first extensive map and 3D structural modelling of lectin-Spike interactions and uncovers candidate receptors involved in Spike binding and SARS-CoV-2 infections. The capacity of CLEC4G and mCD209c lectins to block SARS-CoV-2 viral entry holds promise for pan-variant therapeutic interventions.

molecular biology↗

bioRxiv2018

Renoprotective effects Of Dexmedetomidine against ischemia-reperfusion injury in streptozotocin-induced diabetic rats

BackgroundDiabetic patients are susceptible to renal ischemia-reperfusion injury, which leads to perioperative complications. Nucleotide binding and oligomerization domain (NOD)-like receptor 3 inflammasome participates in the development of diabetes, and contributes to renal ischemia-reperfusion injury. Dexmedetomidine, a highly selective 2-adrenoreceptor agonist, shows renoprotective effects against ischemia-reperfusion injury. We aimed to elucidate the effects, underlying mechanisms, and optimal timing of dexmedetomidine treatment in diabetic rats.\n\nMethodsMale Sprague-Dawley rats (60 animals, weighing 250-300 g) were randomly divided into normal-sham, diabetes-sham, diabetes-ischemia-reperfusion-control, diabetes-ischemia-reperfusion-dexmedetomidine-pre-treatment, and diabetes-ischemia-reperfusion-dexmedetomidine-post-treatment groups. Renal ischemia-reperfusion injury was induced in diabetic rats by occlusion of both renal arteries for 45 minutes followed by reperfusion for 24 hours. Dexmedetomidine (10 g/kg) was administered intraperitoneally 1 hour before ischemia (pre-treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue was biochemically and histopathologically evaluated.\n\nResultsDexmedetomidine treatment attenuated IR-induced increase in NLRP3, caspase-1, IL-1{beta}, phospho-AKT, and phospho-ERK signaling. Moreover, oxidative stress injury, inflammatory reactions, apoptosis, and renal tubular damage were favorably modulated by dexmedetomidine treatment. Furthermore, post-reperfusion treatment with dexmedetomidine was significantly more effective than pre-treatment in modulating inflammasome, AKT and ERK signaling, and oxidative stress.\n\nConclusionsThis study shows that protective effects of dexmedetomidine in renal ischemia-reperfusion injury are preserved in diabetic conditions and may potentially provide a basis for the use of dexmedetomidine in clinical treatment of renal ischemia-reperfusion injury.

pharmacology and toxicology↗