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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.
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COVID-19 , SARS-CoV-2 , República de Corea/epidemiología , Humanos , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , COVID-19/virología , COVID-19/epidemiología , COVID-19/transmisión , Animales , Gatos , Estudios Retrospectivos , Filogenia , Genoma Viral , Enfermedades de los Gatos/virología , Enfermedades de los Gatos/epidemiologíaRESUMEN
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.
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Existing methods for estimating human poses from video content exploit the temporal features of the video sequences and have shown impressive results. However, most methods address spatiotemporal issues separately. They compromise on accuracy to reduce jitter, or require high-resolution images to deal with occlusion, preventing full consideration of temporal features. Unfortunately, these two issues are interrelated. For example, occlusion causes uncertainty between successive frames, leading to unsmoothed results. To address these issues, we propose the Masked Kinematic Continuity-aware Hierarchical Attention Network (M-HANet) as a novel framework that exploits masked kinematic keypoint features by extending our framework HANet framework. First, we randomly select and mask a keypoint to treat the masked keypoint as it is occluded, which allows us to make the network resilient to occlusion. We also use the velocity and acceleration of each individual keypoint to effectively capture temporal features. Second, the proposed hierarchical transformer encoder refines a 2D or 3D input pose derived from existing estimators by aggregating the masked continuity of the spatiotemporal dependencies of human motion. Finally, to facilitate collaborative optimization, we perform an online cross-supervision between the final pose from our decoder and the refined input pose produced by our encoder. We validate the effectiveness of our model demonstrating that our proposed approach improves PCK@0.05 by 14.1% and MPJPE by 8.7 mm compared to the existing method on a variety of tasks, including 2D and 3D pose estimation, body mesh recovery, and sparsely annotated multi-human pose estimation.
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Resiliencia Psicológica , Humanos , Fenómenos Biomecánicos , Movimiento (Física) , IncertidumbreRESUMEN
Ultraviolet light (UV) acts as a powerful disinfectant and can prevent contamination of personal hygiene from various contaminated environments. The 222-nm wavelength of UV-C has a highly effective sterilization activity and is safer than 275-nm UV-C. We investigated the irradiation efficacy of 222-nm UV-C against contaminating bacteria and viruses in liquid and fabric environments. We conducted colony-forming unit assays to determine the number of viable cells and a 50% tissue culture infectious dose assay to evaluate the virus titration. A minimum dose of 27 mJ/cm2 of 222-nm UV-C was required for >95% germicidal activity for gram-negative and -positive bacteria. A 25.1 mJ/cm2 dose could ensure >95% virucidal activity against low-pathogenic avian influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV-2). In addition, this energy dose of 222-nm UV-C effectively inactivated SARS-CoV-2 variants, Delta and Omicron. These results provide valuable information on the disinfection efficiency of 222-nm UV-C in bacterial and virus-contaminated environments and can also develop into a powerful tool for individual hygiene.
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COVID-19 , Enfermedades Transmisibles , Virus , Humanos , SARS-CoV-2 , Rayos Ultravioleta , COVID-19/prevención & control , Virus/efectos de la radiación , Bacterias/efectos de la radiación , Desinfección/métodosRESUMEN
Deformable semi-solid liquid metal particles (LMP) have emerged as a promising substitute for rigid conductive fillers due to their excellent electrical properties and stable conductance under strain. However, achieving a compact and robust coating of LMP on fibers remains a persistent challenge, mainly due to the incompatibility of conventional coating techniques with LMP. Additionally, the limited durability and absence of initial electrical conductivity of LMP restrict their widespread application. In this study, we propose a solution process that robustly and compactly assembles mechanically durable and initially conductive LMP on fibers. Specifically, we present a shearing-based deposition of polymer-attached LMP followed by additional coating with CNT-attached LMP to create bi-layer LMP composite with exceptional durability, electrical conductivity, stretchability, and biocompatibility on various fibers. The versatility and reliability of this manufacturing strategy for 1D electronics are demonstrated through the development of sewn electrical circuits, smart clothes, stretchable biointerfaced fiber, and multifunctional fiber probes.
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Dispositivos Electrónicos Vestibles , Textiles , Reproducibilidad de los Resultados , Polímeros , MetalesRESUMEN
CRISPR-Cas13-mediated viral genome targeting is a novel strategy for defending against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here, we generated mRNA-encoded Cas13b targeting the open reading frame 1b (ORF1b) region to effectively degrade the RNA-dependent RNA polymerase gene. Of the 12 designed CRISPR RNAs (crRNAs), those targeting the pseudoknot site upstream of ORF1b were found to be the most effective in suppressing SARS-CoV-2 propagation. Pseudoknot-targeting Cas13b reduced expression of the spike protein and attenuated viral replication by 99%. It also inhibited the replication of multiple SARS-CoV-2 variants, exhibiting broad potency. We validated the therapeutic efficacy of this system in SARS-CoV-2-infected hACE2 transgenic mice, demonstrating that crRNA treatment significantly reduced viral titers. Our findings suggest that the pseudoknot region is a strategic site for targeted genomic degradation of SARS-CoV-2. Hence, pseudoknot-targeting Cas13b could be a breakthrough therapy for overcoming infections by SARS-CoV-2 or other RNA viruses.
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COVID-19 , Animales , Ratones , SARS-CoV-2/genética , Replicación Viral , ARN Viral/genética , ARN Viral/metabolismoRESUMEN
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 (EC50) 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.
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COVID-19 , Animales , Humanos , SARS-CoV-2 , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Enzima Convertidora de Angiotensina 2 , Antivirales/farmacología , Antivirales/uso terapéutico , Proteínas Tirosina Quinasas/farmacología , Estadios del Ciclo de VidaRESUMEN
A highly contagious virus, severe acute respiratory syndrome coronavirus 2, caused the coronavirus disease 19 (COVID-19) pandemic (SARS-CoV-2). SARS-CoV-2 genetic variants have been reported to circulate throughout the COVID-19 pandemic. COVID-19 symptoms include respiratory symptoms, fever, muscle pain, and breathing difficulty. In addition, up to 30% of COVID-19 patients experience neurological complications such as headaches, nausea, stroke, and anosmia. However, the neurotropism of SARS-CoV-2 infection remains largely unknown. This study investigated the neurotropic patterns between the B1.617.2 (Delta) and Hu-1 variants (Wuhan, early strain) in K18-hACE2 mice. Despite both the variants inducing similar pathogenic patterns in various organs, B1.617.2-infected K18-hACE2 mice demonstrated a higher range of disease phenotypes such as weight loss, lethality, and conjunctivitis when compared to those in Hu-1-infected mice. In addition, histopathological analysis revealed that B1.617.2 infects the brain of K18-hACE2 mice more rapidly and effectively than Hu-1. Finally, we discovered that, in B1.617.2-infected mice, the early activation of various signature genes involved innate cytokines and that the necrosis-related response was most pronounced than that in Hu-1-infected mice. The present findings indicate the neuroinvasive properties of SARS-CoV-2 variants in K18-hACE2 mice and link them to fatal neuro-dissemination during the disease onset.
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COVID-19 , SARS-CoV-2 , Animales , Humanos , Ratones , SARS-CoV-2/genética , PandemiasRESUMEN
Recent state-of-the-art detectors generally exploit the Feature Pyramid Networks (FPN) due to its advantage of detecting objects at different scales. Despite significant advances in object detection owing to the design of feature pyramids, it is still challenging to detect small objects with low resolution and dense distribution in complex scenes. To address these problems, we propose Attentional Feature Pyramid Network, a new feature pyramid architecture named AFPN which consists of three components to enhance the small object detection ability, specifically: Dynamic Texture Attention, Foreground-Aware Co-Attention, and Detail Context Attention. First, Dynamic Texture Attention augments the texture features dynamically by filtering out redundant semantics to highlight small objects in lower layers and amplifying credible details to emphasize large objects in higher layers. Then, Foreground-Aware Co-Attention is explored to detect densely arranged small objects by enhancing the objects feature via foreground-correlated contexts and suppressing the background noise. Finally, to better capture the features of small objects, Detail Context Attention adaptively aggregates detail cues of RoI features with different scales for a more accurate feature representation. By substituting FPN with AFPN in Faster R-CNN, our method performs on par with the state-of-the-art performance on Tsinghua-Tencent 100K. Furthermore, we achieve highly competitive results on small category of both PASCAL VOC and MS COCO.
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Compuestos Orgánicos Volátiles , Atención , Señales (Psicología)RESUMEN
Conventional electronic (e-) skins are a class of thin-film electronics mainly fabricated in laboratories or factories, which is incapable of rapid and simple customization for personalized healthcare. Here a new class of e-tattoos is introduced that can be directly implemented on the skin by facile one-step coating with various designs at multi-scale depending on the purpose of the user without a substrate. An e-tattoo is realized by attaching Pt-decorated carbon nanotubes on gallium-based liquid-metal particles (CMP) to impose intrinsic electrical conductivity and mechanical durability. Tuning the CMP suspension to have low-zeta potential, excellent wettability, and high-vapor pressure enables conformal and intimate assembly of particles directly on the skin in 10 s. Low-cost, ease of preparation, on-skin compatibility, and multifunctionality of CMP make it highly suitable for e-tattoos. Demonstrations of electrical muscle stimulators, photothermal patches, motion artifact-free electrophysiological sensors, and electrochemical biosensors validate the simplicity, versatility, and reliability of the e-tattoo-based approach in biomedical engineering.
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Galio , Nanotubos de Carbono , Tatuaje , Atención a la Salud , Conductividad Eléctrica , Electrónica , Reproducibilidad de los ResultadosRESUMEN
Crude polysaccharides, extracted from two seaweed species (Hizikia fusiforme and Sargassum horneri) and Haliotis discus hannai (abalone) viscera, were evaluated for their inhibitory effect against SARS-CoV-2 propagation. Plaque titration revealed that these crude polysaccharides efficiently inhibited SARS-CoV-2 propagation with IC50 values ranging from 0.35 to 4.37 µg/mL. The crude polysaccharide of H. fusiforme showed the strongest antiviral effect, with IC50 of 0.35 µg/mL, followed by S. horneri and abalone viscera with IC50 of 0.56 and 4.37 µg/mL, respectively. In addition, immunofluorescence assay, western blot, and quantitative RT-PCR analysis verified that these polysaccharides could inhibit SARS-CoV-2 replication. In Vero E6 cells, treatment with these crude polysaccharides before or after viral infection strongly inhibited the expression level of SARS-CoV-2 spikes, nucleocapsid proteins, and RNA copies of RNA-dependent RNA-polymerase and nucleocapsid. These results show that these crude marine polysaccharides effectively inhibit SARS-CoV-2 propagation by interference with viral entry.
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Tratamiento Farmacológico de COVID-19 , Algas Marinas , Antivirales/farmacología , Humanos , Polisacáridos/farmacología , ARN , SARS-CoV-2 , VíscerasRESUMEN
Liquid metal is being regarded as a promising material for soft electronics owing to its distinct combination of high electrical conductivity comparable to that of metals and exceptional deformability derived from its liquid state. However, the applicability of liquid metal is still limited due to the difficulty in simultaneously achieving its mechanical stability and initial conductivity. Furthermore, reliable and rapid patterning of stable liquid metal directly on various soft substrates at high-resolution remains a formidable challenge. In this work, meniscus-guided printing of ink containing polyelectrolyte-attached liquid metal microgranular-particle in an aqueous solvent to generate semi-solid-state liquid metal is presented. Liquid metal microgranular-particle printed in the evaporative regime is mechanically stable, initially conductive, and patternable down to 50 µm on various substrates. Demonstrations of the ultrastretchable (~500% strain) electrical circuit, customized e-skin, and zero-waste ECG sensor validate the simplicity, versatility, and reliability of this manufacturing strategy, enabling broad utility in the development of advanced soft electronics.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against COVID-19. Theses include asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor), and sofosbuvir (an RNA polymerase inhibitor). We found that asunaprevir, but not sofosbuvir and daclatasvir, markedly inhibited SARS-CoV-2-induced cytopathic effects in Vero E6 cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by treatment with asunaprevir. Moreover, asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. A pseudoparticle entry assay revealed that asunaprevir blocked SARS-CoV-2 infection at the binding step of the viral life cycle. Furthermore, asunaprevir inhibited SARS-CoV-2 propagation in human lung Calu-3 cells. Collectively, we found that asunaprevir displays broad-spectrum antiviral activity and therefore might be worth developing as a new drug repurposing candidate for COVID-19.
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Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Isoquinolinas/farmacología , SARS-CoV-2/crecimiento & desarrollo , Sulfonamidas/farmacología , Inhibidores de Proteasa Viral/farmacología , Replicación Viral/efectos de los fármacos , Animales , Carbamatos/farmacología , Línea Celular , Chlorocebus aethiops , ARN Polimerasas Dirigidas por ADN/antagonistas & inhibidores , Células HEK293 , Hepacivirus/efectos de los fármacos , Humanos , Imidazoles/farmacología , Pirrolidinas/farmacología , SARS-CoV-2/efectos de los fármacos , Sofosbuvir/farmacología , Valina/análogos & derivados , Valina/farmacología , Células Vero , Proteínas no Estructurales Virales/antagonistas & inhibidoresRESUMEN
Hybridization of low-dimensional components with diverse geometrical dimensions should offer an opportunity for the discovery of synergistic nanocomposite structures. In this regard, how to establish a reliable interfacial interaction is the key requirement for the successful integration of geometrically different components. Here, we present 1D/2D heterodimensional hybrids via dopant induced hybridization of 2D Ti3C2Tx MXene with 1D nitrogen-doped graphene nanoribbon. Edge abundant nanoribbon structures allow a high level nitrogen doping (â¼6.8 at%), desirable for the strong coordination interaction with Ti3C2Tx MXene surface. For piezoresistive pressure sensor application, strong adhesion between the conductive layers and at the conductive layer/elastomer interface significantly diminishes the sensing hysteresis down to 1.33% and enhances the sensing stability up to 10â¯000 cycles at high pressure (100 kPa). Moreover, large-area pressure sensor array reveals a high potential for smart seat cushion-based posture monitoring application with high accuracy (>95%) by exploiting machine learning algorithm.
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Patient-friendly medical diagnostics and treatments have been receiving a great deal of interest due to their rapid and cost-effective health care applications with minimized risk of infection, which has the potential to replace conventional hospital-based medical procedures. In particular, the integration of recently developed materials into health care devices allows the rapid development of point-of-care (POC) sensing platforms and implantable devices with special functionalities. In this review, the recent advances in biosensors for patient-friendly diagnosis and implantable devices for patient-friendly treatment are discussed. Comprehensive analysis of portable and wearable biosensing platforms for patient-friendly health monitoring and disease diagnosis is provided, including topics such as materials selection, device structure and integration, and biomarker detection strategies. Moreover, specific challenges related to each biological fluid for wearable biosensor-based POC applications are presented. Also, advances in implantable devices, including recent materials development and wireless communication strategies, are discussed. Furthermore, various patient-friendly surgical and treatment approaches are reviewed, such as minimally invasive insertion and mounting, in vivo electrical and optical modulations, and post-operation health monitoring. Finally, the challenges and future perspectives toward the development of the patient-friendly diagnosis and treatment are provided.
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Técnicas Biosensibles , Humanos , Monitoreo Fisiológico , Sistemas de Atención de Punto , Prótesis e ImplantesRESUMEN
Anxiety disorder is known as the most common disease among psychiatric disorders. However, many studies have not been conducted in the Korean medicine area. This study explores the current state of anxiety disorder treatments of Korean medicine through a survey research. The survey for Korean medicine doctors (KMDs) on Korean medicine (KM) diagnosis and treatments for anxiety disorder was conducted online from December 21, 2016, to December 29, 2016. The results were divided into two groups, KMDs and Korean medicine neuropsychiatric specialists (KMNPS), and comparatively analyzed. Self-evaluation and counseling were the most common in both diagnostic methods and evaluation of treatment effects, and KMNPS tended to make extensive use of objective indicators. There was no difference in the rate of psychiatric medication use among the patients between KMD and KMNPS. The main reason for patients wanting KM treatment was the tapering cessation of psychiatric medications. The most common treatments were acupuncture, herbal medicine, and moxibustion, in addition to dry cupping in KMD and psychotherapy in KMNPS. The most important factor for treatment was herbal medicine treatment, followed by rapport formation in KMD and patient's temperament in KMNPS. Opinions on various items were presented as treatment barriers, and KMNPS tended to think more importantly about the patient's family problems. For the items to be additionally trained in the future, KMD chose the diagnostic tools and KMNPS chose psychotherapies. This study is the first study to analyze the clinical patterns for anxiety disorder in KMDs. KMD and KMNPS showed similar patterns in the perception, diagnosis, and treatment of anxiety disorders, but KMNPS tended to use objective indicators and psychotherapy more actively. Further clinical studies for the development of clinical guidelines should be additionally required.
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Passive component-based soft resonators have been spotlighted in the field of wearable and implantable devices due to their remote operation capability and tunable properties. As the output signal of the resonator-based wireless communication device is given in the form of a vector (i.e., a spectrum of reflection coefficient), multiple information can, in principle, be stored and interpreted. Herein, we introduce a device that can deconvolute mechanical stimuli from a single wireless signal using dual-mode operation, specifically enabled by the use of Ti3C2Tx MXene. MXene's strong electromagnetic shielding effect enables the resonator to simultaneously measure pressure and strain without overlapping its output signal, unlike other conductive counterparts that are deficient in shielding ability. Furthermore, convolutional neural-network-based deep learning was implemented to predict the pressure and strain values from unforeseen output wireless signals. Our MXene-integrated wireless device can also be utilized as an on-skin mechanical stimuli sensor for rehabilitation monitoring after orthopedic surgery. The dual-mode signal variation mechanism enabled by integration of MXene allows wireless communication systems to efficiently handle various information simultaneously, through which multistimuli sensing capability can be imparted into passive component-based wearable and implantable electrical devices.
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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.
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Glicoproteínas de Membrana/metabolismo , Secuencia de Aminoácidos , Animales , Línea Celular , Proteínas Ligadas a GPI/química , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/química , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Ratones , Mutagénesis , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Unión Proteica , Dominios Proteicos , Receptores de Superficie Celular/metabolismo , Serina Endopeptidasas/metabolismo , Espermatozoides/metabolismo , Especificidad por Sustrato , Testículo/metabolismoRESUMEN
Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented FGFR1 signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 (SDC1) exhibited typical senescence phenotypes, and those depleted of PAPSS2-, SDC1-, or heparan sulfate 2-O sulfotransferase 1 (HS2ST1) showed decreased FGFR1 internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)-stimulated FGFR1- v-akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin- and caveolin-mediated FGFR1 endocytosis contributed to cellular senescence through the FGFR1-AKT-p53-p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented FGFR1-AKT-p53-p21 signaling, and decreased SDC1 expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of SDC1 expression and FGFR1 internalization, and an increase in FGFR1-AKT-p53-p21 signaling. Together, our results demonstrate that properly sulfated SDC1 plays a critical role in preventing cellular senescence through the regulation of FGFR1 endocytosis.