Biology subjects

Hung, Y.-L.

Publications and source records attributed to Hung, Y.-L..

3 recordsLinked to original sources

bioRxiv2025

Mismatch repair and homologous recombination are yin-yang partners in hybrid zygote meiosis

Rad51 and meiosis-specific Dmc1 catalyze homologous recombination (HR) between maternal and paternal chromosomes during meiosis in many sexual eukaryotes, generating three interhomolog (IH) recombination products: noncrossovers (NCOs), class I crossovers (COs), and class II COs. Some COs form chiasmata, which physically connect homologous chromosomes and ensure proper chromosome segregation during meiosis I. Meiosis is highly relevant to speciation, with the mismatch repair (MMR) system believed to prevent IH-HR, leading to postzygotic isolation between closely related species. We report that several Saccharomyces cerevisiae HR proteins exhibit anti-MMR activities, including Rad51, Rad54, and synapsis-promoting ZMM proteins (Mer3, Zip1, Zip4, and Msh4) in SK1/S288c hybrid zygotes. Srs2 (an ortholog of Escherichia coli helicase UvrD) facilitates MMR by dissembling Rad51-ssDNA presynaptic filaments. Rad51 antagonizes MMR and Srs2 to catalyze D-loop formation. Rad54s anti-MMR activity acts after Srs2 and outcompetes its pro-HR function to promote Rad51-mediated IH-HR in hybrid zygotes. Dmc1 does not possess anti-MMR activity, but exhibits better mismatch tolerability than Rad51. Following D-loop formation mediated by Dmc1 and/or Rad51, ZMM proteins promote class I IH-CO formation while limiting MMR to promote NCO formation by Sgs1 (an ortholog of E. coli RecQ helicase) and prevent class II IH-CO formation by the Mms4*Mus81 endonuclease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/636946v2_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@db6794org.highwire.dtl.DTLVardef@6d5947org.highwire.dtl.DTLVardef@1004489org.highwire.dtl.DTLVardef@938403_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMMR and HR antagonize each other in intraspecies hybrid zygotes. C_LIO_LIThe HR proteins Rad51, Rad54, and ZMM exhibit anti-MMR activities. C_LIO_LIMMR overrides HR in hybrid zygotes with anti-MMR mutations, causing hybrid sterility. C_LI

genetics↗

bioRxiv2024

Cross-institutional HER2 assessment via a computer-aided system using federated learning and stain composition augmentation

The rapid advancement of precision medicine and personalized healthcare has heightened the demand for accurate diagnostic tests. These tests are crucial for administering novel treatments like targeted therapy. To ensure the widespread availability of accurate diagnostics with consistent standards, the integration of computer-aided systems has become essential. Specifically, computer-aided systems that assess biomarker expression have thrusted through the widespread application of deep learning for medical imaging. However, the generalizability of deep learning models has usually diminished significantly when being confronted with data collected from different sources, especially for histological imaging in digital pathology. It has therefore been challenging to effectively develop and employ a computer-aided system across multiple medical institutions. In this study, a biomarker computer-aided framework was proposed to overcome such challenges. This framework incorporated a new approach to augment the composition of histological staining, which enhanced the performance of federated learning models. A HER2 assessment system was developed following the proposed framework, and it was evaluated on a clinical dataset from National Taiwan University Hospital and a public dataset coordinated by the University of Warwick. This assessment system showed an accuracy exceeding 90% for both institutions, whose generalizability outperformed a baseline system developed solely through the clinical dataset by 30%. Compared to previous works where data across different institutions were mixed during model training, the HER2 assessment system achieved a similar performance while it was developed with guaranteed patient privacy via federated learning.

pathology↗

bioRxiv2020

Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 main protease by tafenoquine in vitro

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic, coronavirus disease 2019 (COVID-19), has taken a huge toll on human lives and the global economy. Therefore, effective treatments against this disease are urgently needed. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform to screen compound libraries to identify drugs targeting the SARS-CoV-2 main protease (Mpro), in particular those which are FDA-approved, to be used immediately to treat patients with COVID-19. Mpro has been shown to be one of the most important drug targets among SARS-related coronaviruses as impairment of Mpro blocks processing of viral polyproteins which halts viral replication in host cells. Our findings indicate that the anti-malarial drug tafenoquine (TFQ) induces significant conformational change in SARS-CoV-2 Mpro and diminishes its protease activity. Specifically, TFQ reduces the -helical content of Mpro, which converts it into an inactive form. Moreover, TFQ greatly inhibits SARS-CoV-2 infection in cell culture system. Hence, the current study provides a mechanistic insight into the mode of action of TFQ against SARS-CoV-2 Mpro. Moreover, the low clinical toxicity of TFQ and its strong antiviral activity against SARS-CoV-2 should warrant further testing in clinical trials.

biochemistry↗