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1. Kinematic-aware Hierarchical Attention Network for Human Pose Estimation in Videos

Author

Jin, Kyung-Min, Lim, Byoung-Sung, Lee, Gun-Hee, Kang, Tae-Kyung, and Lee, Seong-Whan

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Previous video-based human pose estimation methods have shown promising results by leveraging aggregated features of consecutive frames. However, most approaches compromise accuracy to mitigate jitter or do not sufficiently comprehend the temporal aspects of human motion. Furthermore, occlusion increases uncertainty between consecutive frames, which results in unsmooth results. To address these issues, we design an architecture that exploits the keypoint kinematic features with the following components. First, we effectively capture the temporal features by leveraging individual keypoint's velocity and acceleration. Second, the proposed hierarchical transformer encoder aggregates spatio-temporal dependencies and refines the 2D or 3D input pose estimated from existing estimators. Finally, we provide an online cross-supervision between the refined input pose generated from the encoder and the final pose from our decoder to enable joint optimization. We demonstrate comprehensive results and validate the effectiveness of our model in various tasks: 2D pose estimation, 3D pose estimation, body mesh recovery, and sparsely annotated multi-human pose estimation. Our code is available at https://github.com/KyungMinJin/HANet.

Published
2022

2. OTPose: Occlusion-Aware Transformer for Pose Estimation in Sparsely-Labeled Videos

Author

Jin, Kyung-Min, Lee, Gun-Hee, and Lee, Seong-Whan

Subjects
Computer Science - Computer Vision and Pattern Recognition, 68T45
Abstract

Although many approaches for multi-human pose estimation in videos have shown profound results, they require densely annotated data which entails excessive man labor. Furthermore, there exists occlusion and motion blur that inevitably lead to poor estimation performance. To address these problems, we propose a method that leverages an attention mask for occluded joints and encodes temporal dependency between frames using transformers. First, our framework composes different combinations of sparsely annotated frames that denote the track of the overall joint movement. We propose an occlusion attention mask from these combinations that enable encoding occlusion-aware heatmaps as a semi-supervised task. Second, the proposed temporal encoder employs transformer architecture to effectively aggregate the temporal relationship and keypoint-wise attention from each time step and accurately refines the target frame's final pose estimation. We achieve state-of-the-art pose estimation results for PoseTrack2017 and PoseTrack2018 datasets and demonstrate the robustness of our approach to occlusion and motion blur in sparsely annotated video data., Comment: 6 pages

Published
2022

3. HTNet: Anchor-free Temporal Action Localization with Hierarchical Transformers

Author

Kang, Tae-Kyung, Lee, Gun-Hee, and Lee, Seong-Whan

Subjects
Computer Science - Computer Vision and Pattern Recognition, 68T45
Abstract

Temporal action localization (TAL) is a task of identifying a set of actions in a video, which involves localizing the start and end frames and classifying each action instance. Existing methods have addressed this task by using predefined anchor windows or heuristic bottom-up boundary-matching strategies, which are major bottlenecks in inference time. Additionally, the main challenge is the inability to capture long-range actions due to a lack of global contextual information. In this paper, we present a novel anchor-free framework, referred to as HTNet, which predicts a set of triplets from a video based on a Transformer architecture. After the prediction of coarse boundaries, we refine it through a background feature sampling (BFS) module and hierarchical Transformers, which enables our model to aggregate global contextual information and effectively exploit the inherent semantic relationships in a video. We demonstrate how our method localizes accurate action instances and achieves state-of-the-art performance on two TAL benchmark datasets: THUMOS14 and ActivityNet 1.3., Comment: 6 pages

Published
2022

7. Joint Dermatological Lesion Classification and Confidence Modeling with Uncertainty Estimation

Author

Lee, Gun-Hee, Ko, Han-Bin, and Lee, Seong-Whan

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Deep learning has played a major role in the interpretation of dermoscopic images for detecting skin defects and abnormalities. However, current deep learning solutions for dermatological lesion analysis are typically limited in providing probabilistic predictions which highlights the importance of concerning uncertainties. This concept of uncertainty can provide a confidence level for each feature which prevents overconfident predictions with poor generalization on unseen data. In this paper, we propose an overall framework that jointly considers dermatological classification and uncertainty estimation together. The estimated confidence of each feature to avoid uncertain feature and undesirable shift, which are caused by environmental difference of input image, in the latent space is pooled from confidence network. Our qualitative results show that modeling uncertainties not only helps to quantify model confidence for each prediction but also helps classification layers to focus on confident features, therefore, improving the accuracy for dermatological lesion classification. We demonstrate the potential of the proposed approach in two state-of-the-art dermoscopic datasets (ISIC 2018 and ISIC 2019).

Published
2021

8. ACNet: Mask-Aware Attention with Dynamic Context Enhancement for Robust Acne Detection

Author

Min, Kyungseo, Lee, Gun-Hee, and Lee, Seong-Whan

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Computer-aided diagnosis has recently received attention for its advantage of low cost and time efficiency. Although deep learning played a major role in the recent success of acne detection, there are still several challenges such as color shift by inconsistent illumination, variation in scales, and high density distribution. To address these problems, we propose an acne detection network which consists of three components, specifically: Composite Feature Refinement, Dynamic Context Enhancement, and Mask-Aware Multi-Attention. First, Composite Feature Refinement integrates semantic information and fine details to enrich feature representation, which mitigates the adverse impact of imbalanced illumination. Then, Dynamic Context Enhancement controls different receptive fields of multi-scale features for context enhancement to handle scale variation. Finally, Mask-Aware Multi-Attention detects densely arranged and small acne by suppressing uninformative regions and highlighting probable acne regions. Experiments are performed on acne image dataset ACNE04 and natural image dataset PASCAL VOC 2007. We demonstrate how our method achieves the state-of-the-art result on ACNE04 and competitive performance with previous state-of-the-art methods on the PASCAL VOC 2007., Comment: 6 pages, 5 figures, SMC 2021

Published
2021

13. Suspected Human-to-Cat Spillover of SARS-CoV-2 Omicron Variant in South Korea.

Author

Yang, Ju-Hee, Oh, Yeonsu, Moon, Sung-Hyun, Lee, Gun-Hee, Kim, Jae-Young, Shin, Yeon-Kyung, Tark, Dongseob, and Cho, Ho-Seong

Subjects
SARS-CoV-2 Omicron variant, ANIMAL populations, ANIMAL tracks, SARS-CoV-2
Abstract

This retrospective study reports the isolation and characterization of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) from a household cat in South Korea. The cat, which was presented with respiratory symptoms, was identified during a retrospective analysis of samples collected between April 2021 and March 2022. Genomic sequencing revealed that the isolated virus belonged to the Omicron variant (BA.1), coinciding with its global emergence in early 2022. This case study provides evidence for the potential of direct human-to-cat transmission of the Omicron variant in South Korea during its period of widespread circulation. Our findings underscore the importance of continuous monitoring of SARS-CoV-2 in both human and animal populations to track viral evolution and potential spillover events. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Kinematic-aware Hierarchical Attention Network for Human Pose Estimation in Videos

Author

Jin, Kyung-Min, Lim, Byoung-Sung, Lee, Gun-Hee, Kang, Tae-Kyung, and Lee, Seong-Whan

Subjects
FOS: Computer and information sciences, Computer Vision and Pattern Recognition (cs.CV), Computer Science - Computer Vision and Pattern Recognition
Abstract

Previous video-based human pose estimation methods have shown promising results by leveraging aggregated features of consecutive frames. However, most approaches compromise accuracy to mitigate jitter or do not sufficiently comprehend the temporal aspects of human motion. Furthermore, occlusion increases uncertainty between consecutive frames, which results in unsmooth results. To address these issues, we design an architecture that exploits the keypoint kinematic features with the following components. First, we effectively capture the temporal features by leveraging individual keypoint's velocity and acceleration. Second, the proposed hierarchical transformer encoder aggregates spatio-temporal dependencies and refines the 2D or 3D input pose estimated from existing estimators. Finally, we provide an online cross-supervision between the refined input pose generated from the encoder and the final pose from our decoder to enable joint optimization. We demonstrate comprehensive results and validate the effectiveness of our model in various tasks: 2D pose estimation, 3D pose estimation, body mesh recovery, and sparsely annotated multi-human pose estimation. Our code is available at https://github.com/KyungMinJin/HANet.

Published
2023

22. PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins

Author

Lee, Gun Hee, 1000030532056, Fujita, Morihisa, Nakanishi, Hideki, 1000050604732, Miyata, Haruhiko, 1000020304066, Ikawa, Masahito, 1000000294124, Maeda, Yusuke, 1000000304048, Murakami, Yoshiko, Kinoshita, Taroh, Lee, Gun Hee, 1000030532056, Fujita, Morihisa, Nakanishi, Hideki, 1000050604732, Miyata, Haruhiko, 1000020304066, Ikawa, Masahito, 1000000294124, Maeda, Yusuke, 1000000304048, Murakami, Yoshiko, and Kinoshita, Taroh

Abstract

Gun-Hee Lee, Morihisa Fujita, Hideki Nakanishi, Haruhiko Miyata, Masahito Ikawa, Yusuke Maeda, Yoshiko Murakami, Taroh Kinoshita, PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins, Journal of Biological Chemistry, Volume 295, Issue 42, 2020, Pages 14501-14509, ISSN 0021-9258, https://doi.org/10.1074/jbc.RA120.014643., PGAP6, also known as TMEM8A, is a phospholipase A2 with specificity to glycosylphosphatidylinositol (GPI) and expressed on the surface of various cells. CRIPTO, a GPI-anchored co-receptor for a morphogenic factor Nodal, is a sensitive substrate of PGAP6. PGAP6-mediated shedding of CRIPTO plays a critical role in an early stage of embryogenesis. In contrast, CRYPTIC, a close family member of CRIPTO, is resistant to PGAP6. In this report, chimeras between CRIPTO and CRYPTIC and truncate mutants of PGAP6 were used to demonstrate that the Cripto-1/FRL1/Cryptic domain of CRIPTO is recognized by an N-terminal domain of PGAP6 for processing. We also report that among 56 human GPI-anchored proteins tested, only glypican 3, prostasin, SPACA4, and contactin-1, in addition to CRIPTO, are sensitive to PGAP6, indicating that PGAP6 has a narrow specificity toward various GPI-anchored proteins.

Published
2020

25. A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

Author

Lee, Gun Hee, 1000030532056, Fujita, Morihisa, 1000090551044, Takaoka, Katsuyoshi, 1000000304048, Murakami, Yoshiko, 1000070578848, Fujihara, Yoshitaka, 1000040452461, Kanzawa, Noriyuki, Murakami, Kei-Ichi, Kajikawa, Eriko, Takada, Yoko, Saito, Kazunobu, 1000020304066, Ikawa, Masahito, 1000000208589, Hamada, Hiroshi, 1000000294124, Maeda, Yusuke, 1000010153165, Kinoshita, Taroh, Lee, Gun Hee, 1000030532056, Fujita, Morihisa, 1000090551044, Takaoka, Katsuyoshi, 1000000304048, Murakami, Yoshiko, 1000070578848, Fujihara, Yoshitaka, 1000040452461, Kanzawa, Noriyuki, Murakami, Kei-Ichi, Kajikawa, Eriko, Takada, Yoko, Saito, Kazunobu, 1000020304066, Ikawa, Masahito, 1000000208589, Hamada, Hiroshi, 1000000294124, Maeda, Yusuke, 1000010153165, and Kinoshita, Taroh

Abstract

©2016 Gun-Hee Lee et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.201605121, Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRI PTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRY PTIC, a close homologue of CRI PTO, is not sensitive. CRI PTO processed by PGAP6 was released as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D. CRI PTO shed by PGAP6 was active as a coreceptor in Nodal signaling, whereas cell-associated CRI PTO activity was reduced when PGAP6 was expressed. Homozygous Pgap6 knockout mice showed defects in early embryonic development, particularly in the formation of the anterior-posterior axis, which are common features with Cripto knockout embryos. These results suggest PGAP6 plays a critical role in Nodal signaling modulation through CRI PTO shedding.

Published
2016

26. Preparation and Evaluation of Poly(Ethylene Glycol)-B-Poly(Caprolactone) Diblock Copolymers with Zwitterionic End Group for Thermo-Responsive Properties

Author

Lee, Bo Keun, Kwon, Doo Yeon, Park, Ji Hoon, Lee, Gun Hee, Baek, Ji Hye, Chun, Heung Jae, Koh, Young Joo, and Kim, Moon Suk

Subjects
immune system diseases, technology, industry, and agriculture, musculoskeletal system
Abstract

Thermo-responsive materials are viscoelastic materials that undergo a sol-to-gel phase transition at a specific temperature and many materials have been developed. MPEG-b-PCL (MPC) as a thermo-responsive material contained hydrophilic and hydrophobic segments and it formed an ordered crystalline structure of hydrophobic PCL segments in aqueous solutions. The ordered crystalline structure packed tightly or aggregated and finally induced an aggregated gel through intra- and inter-molecular interactions as a function of temperature. Thus, we introduced anionic and cationic groups into the end positions of the PCL chain to alter the hydrophobicity of the PCL segment. Introducing anionic and cationic groups into the PCL end position altered their solubility by changing the crystallinity and hydrophobicity of the PCL block domains. These results indicated that the properties of the end group in the hydrophobic PCL blockand the balance between hydrophobicity and hydrophilicity affect thermo-responsivebehavior of the copolymers in aqueous solutions. Thus, we concluded that determinant of the temperature-dependent thermo-responsive behavior of MPC depend on the ionic end group in the PCL block. So, we introduced zwitterionic end groups to investigate the thermo-responsive behavior of MPC. Methoxypoly(ethylene oxide) and ε-caprolactone (CL) were randomly copolymerized that introduced varying hydrophobic PCL lengths and an MPC featuring a zwitterionic sulfobetaine (MPC-ZW) at the chain end of the PCL segment. The MPC and MPC-ZW copolymers were obtained formed sol-state at room temperature when prepared as 20-wt% aqueous solutions. The solubility of MPC decreased when the PCL block was increased from molecular weight. The solubilization time of MPC-2.4k was around 20 min and MPC-2.8k, MPC-3.0k increased to 30 min and 1 h, respectively. MPC-3.6k was not solubilized. In case of MPC-ZW 3.6k, However, the zwitterion-modified MPC copolymers were solubilized in 3–5 min. This result indicates that the zwitterionic end group of the MPC-ZW diblock copolymer increased the aqueous solubility of the diblock copolymer even when the length of the hydrophobic PCL segment was increased. MPC and MPC-ZW diblock copolymers that featuring zwitterionic end groups were synthesized successfully. The sol-to-gel phase-transition was formed that specific temperature depend on the length of the PCL hydrophobic segments introduced and on the zwitterion groups attached to the MPC chain end. This result indicated that the zwitterionic end groups reduced the hydrophobicity in the PCL block and changed the solubilization. The MPC-ZW diblock copolymer can be utilized as a potential injectable drug and cell carrier.

Published
2014
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27. A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

Author

Lee, Gun-Hee, primary, Fujita, Morihisa, additional, Takaoka, Katsuyoshi, additional, Murakami, Yoshiko, additional, Fujihara, Yoshitaka, additional, Kanzawa, Noriyuki, additional, Murakami, Kei-ichi, additional, Kajikawa, Eriko, additional, Takada, Yoko, additional, Saito, Kazunobu, additional, Ikawa, Masahito, additional, Hamada, Hiroshi, additional, Maeda, Yusuke, additional, and Kinoshita, Taroh, additional

Published
2016
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35. PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins

Author

Lee, Gun Hee, Fujita, Morihisa, Nakanishi, Hideki, Miyata, Haruhiko, Ikawa, Masahito, Maeda, Yusuke, Murakami, Yoshiko, Kinoshita, Taroh, Lee, Gun Hee, Fujita, Morihisa, Nakanishi, Hideki, Miyata, Haruhiko, Ikawa, Masahito, Maeda, Yusuke, Murakami, Yoshiko, and Kinoshita, Taroh

Abstract

PGAP6, also known as TMEM8A, is a phospholipase A2 with specificity to glycosylphosphatidylinositol (GPI) and expressed on the surface of various cells. CRIPTO, a GPI-anchored co-receptor for a morphogenic factor Nodal, is a sensitive substrate of PGAP6. PGAP6-mediated shedding of CRIPTO plays a critical role in an early stage of embryogenesis. In contrast, CRYPTIC, a close family member of CRIPTO, is resistant to PGAP6. In this report, chimeras between CRIPTO and CRYPTIC and truncate mutants of PGAP6 were used to demonstrate that the Cripto-1/FRL1/Cryptic domain of CRIPTO is recognized by an N-terminal domain of PGAP6 for processing. We also report that among 56 human GPI-anchored proteins tested, only glypican 3, prostasin, SPACA4, and contactin-1, in addition to CRIPTO, are sensitive to PGAP6, indicating that PGAP6 has a narrow specificity toward various GPI-anchored proteins., Gun-Hee Lee, Morihisa Fujita, Hideki Nakanishi, Haruhiko Miyata, Masahito Ikawa, Yusuke Maeda, Yoshiko Murakami, Taroh Kinoshita, PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins, Journal of Biological Chemistry, Volume 295, Issue 42, 2020, Pages 14501-14509, ISSN 0021-9258, https://doi.org/10.1074/jbc.RA120.014643.

36. A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

Author

Lee, Gun Hee, Fujita, Morihisa, Takaoka, Katsuyoshi, Murakami, Yoshiko, Fujihara, Yoshitaka, Kanzawa, Noriyuki, Murakami, Kei-Ichi, Kajikawa, Eriko, Takada, Yoko, Saito, Kazunobu, Ikawa, Masahito, Hamada, Hiroshi, Maeda, Yusuke, Kinoshita, Taroh, Lee, Gun Hee, Fujita, Morihisa, Takaoka, Katsuyoshi, Murakami, Yoshiko, Fujihara, Yoshitaka, Kanzawa, Noriyuki, Murakami, Kei-Ichi, Kajikawa, Eriko, Takada, Yoko, Saito, Kazunobu, Ikawa, Masahito, Hamada, Hiroshi, Maeda, Yusuke, and Kinoshita, Taroh

Abstract

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRI PTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRY PTIC, a close homologue of CRI PTO, is not sensitive. CRI PTO processed by PGAP6 was released as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D. CRI PTO shed by PGAP6 was active as a coreceptor in Nodal signaling, whereas cell-associated CRI PTO activity was reduced when PGAP6 was expressed. Homozygous Pgap6 knockout mice showed defects in early embryonic development, particularly in the formation of the anterior-posterior axis, which are common features with Cripto knockout embryos. These results suggest PGAP6 plays a critical role in Nodal signaling modulation through CRI PTO shedding., ©2016 Gun-Hee Lee et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.201605121

37. PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins

Author

Lee, Gun Hee, Fujita, Morihisa, Nakanishi, Hideki, Miyata, Haruhiko, Ikawa, Masahito, Maeda, Yusuke, Murakami, Yoshiko, Kinoshita, Taroh, Lee, Gun Hee, Fujita, Morihisa, Nakanishi, Hideki, Miyata, Haruhiko, Ikawa, Masahito, Maeda, Yusuke, Murakami, Yoshiko, and Kinoshita, Taroh

Abstract

Gun-Hee Lee, Morihisa Fujita, Hideki Nakanishi, Haruhiko Miyata, Masahito Ikawa, Yusuke Maeda, Yoshiko Murakami, Taroh Kinoshita, PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins, Journal of Biological Chemistry, Volume 295, Issue 42, 2020, Pages 14501-14509, ISSN 0021-9258, https://doi.org/10.1074/jbc.RA120.014643., PGAP6, also known as TMEM8A, is a phospholipase A2 with specificity to glycosylphosphatidylinositol (GPI) and expressed on the surface of various cells. CRIPTO, a GPI-anchored co-receptor for a morphogenic factor Nodal, is a sensitive substrate of PGAP6. PGAP6-mediated shedding of CRIPTO plays a critical role in an early stage of embryogenesis. In contrast, CRYPTIC, a close family member of CRIPTO, is resistant to PGAP6. In this report, chimeras between CRIPTO and CRYPTIC and truncate mutants of PGAP6 were used to demonstrate that the Cripto-1/FRL1/Cryptic domain of CRIPTO is recognized by an N-terminal domain of PGAP6 for processing. We also report that among 56 human GPI-anchored proteins tested, only glypican 3, prostasin, SPACA4, and contactin-1, in addition to CRIPTO, are sensitive to PGAP6, indicating that PGAP6 has a narrow specificity toward various GPI-anchored proteins.

38. A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

Author

Lee, Gun Hee, Fujita, Morihisa, Takaoka, Katsuyoshi, Murakami, Yoshiko, Fujihara, Yoshitaka, Kanzawa, Noriyuki, Murakami, Kei-Ichi, Kajikawa, Eriko, Takada, Yoko, Saito, Kazunobu, Ikawa, Masahito, Hamada, Hiroshi, Maeda, Yusuke, Kinoshita, Taroh, Lee, Gun Hee, Fujita, Morihisa, Takaoka, Katsuyoshi, Murakami, Yoshiko, Fujihara, Yoshitaka, Kanzawa, Noriyuki, Murakami, Kei-Ichi, Kajikawa, Eriko, Takada, Yoko, Saito, Kazunobu, Ikawa, Masahito, Hamada, Hiroshi, Maeda, Yusuke, and Kinoshita, Taroh

Abstract

©2016 Gun-Hee Lee et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.201605121, Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRI PTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRY PTIC, a close homologue of CRI PTO, is not sensitive. CRI PTO processed by PGAP6 was released as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D. CRI PTO shed by PGAP6 was active as a coreceptor in Nodal signaling, whereas cell-associated CRI PTO activity was reduced when PGAP6 was expressed. Homozygous Pgap6 knockout mice showed defects in early embryonic development, particularly in the formation of the anterior-posterior axis, which are common features with Cripto knockout embryos. These results suggest PGAP6 plays a critical role in Nodal signaling modulation through CRI PTO shedding.

39. Evaluation of vaccine efficacy with 2B/T epitope conjugated porcine IgG-Fc recombinants against foot-and-mouth disease virus.

Author

Song BM, Lee GH, Kang SM, and Tark D

Subjects
Animals, Swine, Guinea Pigs, Vaccine Efficacy, Swine Diseases prevention & control, Swine Diseases immunology, Swine Diseases virology, Epitopes, T-Lymphocyte immunology, Recombinant Proteins immunology, Epitopes, B-Lymphocyte immunology, Female, Immunoglobulin Fc Fragments immunology, Foot-and-Mouth Disease Virus immunology, Foot-and-Mouth Disease prevention & control, Foot-and-Mouth Disease immunology, Viral Vaccines immunology, Vaccines, Synthetic immunology, Immunoglobulin G blood, Immunoglobulin G immunology, Antibodies, Viral blood, Antibodies, Viral immunology
Abstract

The inactivated vaccine is effective in controlling foot-and-mouth disease (FMD), but it has drawbacks such as the need for a biosafety level 3 laboratory facility to handle live foot-and-mouth disease virus (FMDV), high production costs, and biological safety risks. In response to these challenges, we developed a new recombinant protein vaccine (2BT-pIgG-Fc) containing porcine IgG-Fc to enhance protein stability in the body. This vaccine incorporates two-repeat B-cell and one-single T-cell epitope derived from O/Jincheon/SKR/2014. Our study confirmed that 2BT-pIgG-Fc and a commercial FMDV vaccine induced FMDV-specific antibodies in guinea pigs at 28 days post-vaccination. The percentage inhibition (PI) value of 2BT-pIgG-Fc was 90.43%, and the commercial FMDV vaccine was 81.75%. The PI value of 2BT-pIgG-Fc was 8.68% higher than that of commercial FMDV vaccine. In pigs, the primary target animals for FMDV, all five individuals produced FMDV-specific antibodies 42 days after vaccination with 2BT-pIgG-Fc. Furthermore, serum from 2BT-pIgG-Fc-vaccinated pigs exhibited neutralizing ability against FMDV infection. Intriguingly, the 2BT-pIgG-Fc recombinant demonstrated FMDV-specific antibody production rates and neutralization efficiency similar to commercial inactivated vaccines. This study illustrates the potential to enhance vaccine efficacy by strategically combining well-known antigenic domains in the development of recombinant protein-based vaccines.

Published
2024
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40. Amuvatinib Blocks SARS-CoV-2 Infection at the Entry Step of the Viral Life Cycle.

Author

Huynh TTX, Pham TX, Lee GH, Lee JB, Lee SG, Tark D, Lim YS, and Hwang SB

Subjects
Animals, Humans, SARS-CoV-2, Imatinib Mesylate pharmacology, Imatinib Mesylate therapeutic use, Angiotensin-Converting Enzyme 2, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Protein-Tyrosine Kinases pharmacology, Life Cycle Stages, COVID-19
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 propagation is mediated by the protein interaction between viral proteins and host cells. Tyrosine kinase has been implicated in viral replication, and hence, it has become a target for developing antiviral drugs. We have previously reported that receptor tyrosine kinase inhibitor blocks the replication of hepatitis C virus (HCV). In the present study, we investigated two receptor tyrosine kinase-specific inhibitors, amuvatinib and imatinib, for their potential antiviral efficacies against SARS-CoV-2. Treatment with either amuvatinib or imatinib displays an effective inhibitory activity against SARS-CoV-2 propagation without an obvious cytopathic effect in Vero E6 cells. Notably, amuvatinib exerts a stronger antiviral activity than imatinib against SARS-CoV-2 infection. Amuvatinib blocks SARS-CoV-2 infection with a 50% effective concentration (EC 50 ) value ranging from ~0.36 to 0.45 μM in Vero E6 cells. We further demonstrate that amuvatinib inhibits SARS-CoV-2 propagation in human lung Calu-3 cells. Using pseudoparticle infection assay, we verify that amuvatinib blocks SARS-CoV-2 at the entry step of the viral life cycle. More specifically, amuvatinib inhibits SARS-CoV-2 infection at the binding-attachment step. Moreover, amuvatinib exhibits highly efficient antiviral activity against emerging SARS-CoV-2 variants. Importantly, we demonstrate that amuvatinib inhibits SARS-CoV-2 infection by blocking ACE2 cleavage. Taken together, our data suggest that amuvatinib may provide a potential therapeutic agent for the treatment of COVID-19. IMPORTANCE Tyrosine kinase has been implicated in viral replication and has become an antiviral drug target. Here, we chose two well-known receptor tyrosine kinase inhibitors, amuvatinib and imatinib, and evaluated their drug potencies against SARS-CoV-2. Surprisingly, amuvatinib displays a stronger antiviral activity than imatinib against SARS-CoV-2. Amuvatinib blocks SARS-CoV-2 infection by inhibiting ACE2 cleavage and the subsequent soluble ACE2 receptor. All these data suggest that amuvatinib may be a potential therapeutic agent in SARS-CoV-2 prevention for those experiencing vaccine breakthroughs., Competing Interests: The authors declare no conflict of interest.

Published
2023
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