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This study examined the relationships between marketing exposure, in-game purchase, problem gaming, online simulated gambling game playing, and psychological distress. Data were obtained from a sample of 2,595 seventh-grade students from 30 middle schools in Taiwan. A self-administered questionnaire was conducted in 2020. The results indicated that 94% of adolescents engage in online gaming, with 38% making in-game purchases, and 9% playing online simulated gambling games. The multiple regression results showed that adolescents who are exposed to higher levels of gaming marketing, influenced by advertising effects, involved in in-game purchases, and have lower levels of active parental mediation were more likely to experience problem gaming. Adolescents who have increased exposure to gambling game marketing, are influenced by advertising effects, are involved in in-game purchases, and who are experiencing problem gaming were more likely to engage in online simulated gambling game playing and token purchasing. Involvement in in-game purchases, problem gaming, and playing online simulated gambling games were associated with higher levels of psychological distress and poor sleep quality. In conclusion, the results of this study link adolescents' exposure to marketing with their involvement in in-game purchases, problem gaming, and engaging in online simulated gambling.
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[This corrects the article DOI: 10.1371/journal.pone.0278290.].
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Bacterial pore-forming toxins (PFTs) that disrupt host plasma membrane integrity (PMI) significantly contribute to the virulence of various pathogens. However, how host cells protect PMI in response to PFT perforation in vivo remains obscure. Previously, we demonstrated that the HLH-30/TFEB-dependent intrinsic cellular defense (INCED) is elicited by PFT to maintain PMI in Caenorhabditis elegans intestinal epithelium. Yet, the molecular mechanism for the full activation of HLH-30/TFEB by PFT remains elusive. Here, we reveal that PRMT-7 (protein arginine methyltransferase-7) is indispensable to the nuclear transactivation of HLH-30 elicited by PFTs. We demonstrate that PRMT-7 participates in the methylation of HLH-30 on its RAG complex binding domain to facilitate its nuclear localization and activation. Moreover, we showed that PRMT7 is evolutionarily conserved to regulate TFEB cellular localization and repair plasma damage caused by PFTs in human intestinal cells. Together, our observations not only unveil a novel PRMT-7/PRMT7-dependent post-translational regulation of HLH-30/TFEB but also shed insight on the evolutionarily conserved mechanism of the INCED against PFT in metazoans.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Proteínas de Caenorhabditis elegans , Membrana Celular , Proteína-Arginina N-Metiltransferases , Proteína-Arginina N-Metiltransferases/metabolismo , Membrana Celular/metabolismo , Humanos , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidade , Metilação , Células HEK293 , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
In this study, we examined the relationships between the use of online dating applications (apps), online victimization, and psychosocial distress among adolescents. This study was conducted in 2020. A sample of 2595 seventh-grade students from 30 Taiwanese middle schools was surveyed. We conducted a self-administered survey. Overall, 15% of the adolescents reported using online dating apps in the past year, while 78% reported having seen dating app advertisements on the internet in the past year. Multivariate analysis results indicated that adolescents' exposure to the marketing of dating apps and poor academic performance were both associated with the use of online dating apps. Adolescents who used dating apps were more likely to experience online privacy victimization, cyberbullying victimization, and online sexual harassment. The use of dating apps by adolescents, online privacy victimization, cyberbullying victimization, and online sexual harassment were associated with higher levels of depression, anxiety, and stress. In conclusion, adolescent use of dating apps is related to online victimization and psychological distress.
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A high-salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity and mortality, remains unknown. Here, we report that HSD impairs long-term brain recovery after intracerebral hemorrhage, a severe form of stroke, despite salt withdrawal prior to the injury. Mechanistically, HSD induces innate immune priming and training in hematopoietic stem and progenitor cells (HSPCs) by downregulation of NR4a family and mitochondrial oxidative phosphorylation. This training compromises alternative activation of monocyte-derived macrophages (MDMs) without altering the initial inflammatory responses of the stroke brain. Healthy mice transplanted with bone marrow from HSD-fed mice retain signatures of reduced MDM reparative functions, further confirming a persistent form of innate immune memory that originates in the bone marrow. Loss of NR4a1 in macrophages recapitulates HSD-induced negative impacts on stroke outcomes while gain of NR4a1 enables stroke recovery in HSD animals. Together, we provide the first evidence that links HSD-induced innate immune memory to the acquisition of persistent dysregulated inflammatory responses and unveils NR4a1 as a potential therapeutic target.
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Acidente Vascular Cerebral , Imunidade Treinada , Camundongos , Animais , Macrófagos , Inflamação , Cloreto de Sódio na Dieta/efeitos adversos , Dieta , Imunidade InataRESUMO
In this study, we examined influencer marketing and consumption of non-alcoholic beer by adolescents to determine how these factors could affect the intentions of adolescents to purchase and drink alcohol. A total of 3121 high-school students recruited from 36 schools in Taiwan completed a self-administered questionnaire during the COVID-19 pandemic in 2022. The results indicate that 19% of these adolescents consumed non-alcoholic beer and 28% consumed alcohol in the past year. Multivariate analysis positively associated adolescents' exposure to influencer marketing with their purchase and consumption of non-alcoholic beer. Adolescents' exposure to influencer marketing of non-alcoholic beer combined with lower levels of parental restrictive mediation was associated with increased odds of the purchase and consumption of alcohol. For individuals who did not purchase alcohol in the past year, both the exposure to influencer marketing and the consumption of non-alcoholic beer were associated with intending to purchase alcohol in the future. Similarly, individuals who previously abstained from the consumption of alcohol, both the exposure to influencer marketing and the consumption of non-alcoholic beer were associated with intending to consume alcohol. In conclusion, when adolescents were exposed to influencer marketing of non-alcoholic beer they were more likely to consume it, which resulted in an increased likelihood that they would then purchase and consume alcohol.
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This study examined the relationships between children's mobile gaming preferences, online risks, and mental health. Data were obtained from a sample of 2,702 third and fourth grade students from 16 elementary schools in Taiwan and 9 schools in China. A self-administered questionnaire was used. The mental state of the children who participated in the study was assessed using the Strengths and Difficulties Questionnaire (SDQ), while mobile gaming addiction was assessed using the short form of the Internet Gaming Disorders Scale (IGDS9-SF). The results showed that about 54% of children played mobile games with others (multi-player), while 31% played mobile games alone, and 15% did not play mobile games. Multiple logistic regression results indicated that behaviors such as participating in multi-player games, playing violent games, a poor parent-child relationship, and living in a rural area were associated with a greater risk of mobile gaming addiction. Involvement in multi-player games, playing violent games, mobile gaming addiction, and exposure to mobile violence/pornography were associated with greater risks of cyber aggression/victimization. Multiple regression results showed that being a multi-player, playing violent games, mobile gaming addiction, exposure to violence/pornography, exposure to cyber aggression/victimization, and having a poor parent-child relationship were associated with emotional and behavioral problems.
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Cyberbullying , Aplicativos Móveis , Jogos de Vídeo , Humanos , Saúde Mental , AgressãoRESUMO
In this study, we examined excessive online gaming by adolescents and the resultant effects of their exposure to the online marketing of energy drinks and alcohol, and whether marketing literacy could serve as a mitigating factor. This cross-sectional study was conducted in 2020. Data were obtained from a sample of 2613 seventh-grade students from 30 middle schools in Taiwan. A self-administered questionnaire was conducted. The results showed that nearly 18% of the adolescent respondents had used energy drinks, while 75% reported seeing energy-drink advertisements on the internet in the past year. Multiple regression results indicated that factors such as being male, reporting excessive gaming, being exposed to higher levels of online energy-drink marketing, and reporting alcohol use were positively associated with energy-drink consumption. A higher level of online energy-drink marketing-affective literacy, however, was negatively associated with energy-drink consumption. In conclusion, factors that predicted energy-drink consumption among adolescents included excessive gaming and exposure to online energy-drink marketing, but marketing-affective literacy tended to lessen the impact of such advertising.
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Bebidas Energéticas , Jogos de Vídeo , Adolescente , Publicidade , Estudos Transversais , Feminino , Humanos , Masculino , Marketing/métodosRESUMO
BACKGROUND: In this study we examined the phenomena of smartphone addiction, online harassment, and school bullying/victimization to predict the prospective influence these could have on the onset and persistence of sleep problems and depression among children. METHODS: Responses from 2155 fifth-grade children recruited from 30 primary schools in Taipei were assessed, and a follow-up was performed in the 6th grade. Self-administered questionnaires were collected for each year. FINDINGS: Children who reported smartphone addictions, online harassment, and school bullying/victimization coupled with an increase in those factors were more likely to experience the onset and persistence of sleep problems. In addition, children who reported smartphone addiction, online harassment, school bullying/victimization, and poor sleep quality were more likely to experience the onset and persistence of depression. IMPLICATIONS: School nurses or pediatric nurses should be able to assess children's Internet use and risks to understand potential influences on sleep quality and mental status and provide recommendations for children, parents and schools.
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Bullying , Vítimas de Crime , Transtornos do Sono-Vigília , Criança , Depressão/diagnóstico , Depressão/epidemiologia , Humanos , Transtorno de Adição à Internet , Estudos Prospectivos , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , SmartphoneRESUMO
BACKGROUND: The detection rate of Barcelona Clinic Liver Cancer (BCLC) very-early-stage hepatocellular carcinoma (HCC) is increasing because of advances in surveillance and improved imaging technologies for high-risk populations. Surgical resection (SR) and radiofrequency ablation (RFA) are both first-line treatments for very-early-stage HCC, but the differences in clinical outcomes between patients treated with SR and RFA remain unclear. This study investigated the prognosis of SR and RFA for very-early-stage HCC patients with long-term follow-up. METHODS: This study was retrospectively collected data on the clinicopathological characteristics, overall survival (OS), and disease-free survival (DFS) of 188 very-early-stage HCC patients (≤ 2 cm single HCC). OS and DFS were analyzed using the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. RESULTS: Of the 188 HCC patients, 103 received SR and 85 received RFA. The median follow-up time was 56 months. The SR group had significantly higher OS than the RFA group (10-year cumulative OS: 55.2% and 31.3% in the SR and RFA groups, respectively). No statistically significant difference was observed in DFS between the SR and RFA groups (10-year cumulative DFS: 45.9% and 32.6% in the SR and RFA groups, respectively). After PSM, the OS in the SR group remained significantly higher than that in the RFA group (10-year cumulative OS: 54.7% and 42.2% in the SR and RFA groups, respectively). No significant difference was observed in DFS between the SR and RFA groups (10-year cumulative DFS: 43.0% and 35.4% in the SR and RFA groups, respectively). Furthermore, in the multivariate Cox regression analysis, treatment type (hazard ratio (HR): 0.54, 95% confidence interval (CI): 0.31-0.95; P = 0.032) and total bilirubin (HR: 1.92; 95% CI: 1.09-3.41; P = 0.025) were highly associated with OS. In addition, age (HR: 2.14, 95% CI: 1.36-3.36; P = 0.001) and cirrhosis (HR: 1.79; 95% CI: 1.11-2.89; P = 0.018) were strongly associated with DFS. CONCLUSION: For patients with very-early-stage HCC, SR was associated with significantly higher OS rates than RFA. However, no significant difference was observed in DFS between the SR and RFA groups.
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Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Pontuação de Propensão , Ablação por Radiofrequência/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Beyond its well-known canonical function as a tumor suppressor, p53 is also involved in numerous cellular processes through altered transcription under both normal and pathological conditions. The functional diversity of p53 outputs is complex and dependent on cell context. However, the underlying mechanisms responsible for this diversity remain largely unclear. The emerging evidence of p53 mutations involved in regulating endocytic trafficking and signaling, in tandem to promote malignancy (invasion, exosome biogenesis and immune evasion), sheds light on possible mechanisms behind the p53-driven complexity. The interrelated nature of endocytic trafficking and receptor signaling that form dynamic and adaptable feedback loops - either positive or negative - functions to modulate multiple cellular outputs. Biasing the tunable endocytic trafficking and receptor signaling network by mutant p53 expands the purview of p53, allowing its contribution to diverse and aggressive phenotypes. In this review, we explore recent studies in which the novel role of mutant p53 in altering endocytic trafficking to bias receptor signaling and drive transforming phenotypes is revealed. Understanding the complex crosstalk of mutant p53, endocytic trafficking and receptor signaling will allow the development of therapies to selectively target p53-altered endocytic processes.
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Endocitose/genética , Mutação com Ganho de Função , Integrina beta1/genética , Neoplasias Pulmonares/genética , Proteína Supressora de Tumor p53/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/imunologia , Endossomos/genética , Endossomos/metabolismo , Receptores ErbB/genética , Receptores ErbB/imunologia , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina beta1/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Ribonuclease III/genética , Ribonuclease III/imunologia , Transdução de Sinais , Evasão Tumoral , Proteína Supressora de Tumor p53/imunologiaRESUMO
This study assessed the discrepancies between reports from parents and children concerning children's exposure to violence/pornography on mobile devices and the impact on the psychosocial adjustment of children. Data were obtained from a sample of 2,230 parent-child dyads recruited from 16 elementary schools (1,140 dyads) in Taiwan and 9 schools (1,090 dyads) in China. A self-administered questionnaire was used. The results showed that about 30 percent of children reported being exposed to violence on mobile devices. Approximately 70 percent of their parents were unaware of their child's exposure to violence on mobile devices. About 16 percent of children reported exposure to pornography on mobile devices, and 80 percent of their parents were unaware of this exposure. Multinomial logistic regression results showed that after controlling for parent and child sociodemographic variables, factors related to parental unawareness of child exposure to violence on mobile devices included a child's ownership of mobile devices, smartphone/tablet use time, a lower level of parental understanding, and a residence in China or in a rural area, whereas the parent-child relationship and a child's smartphone/tablet use time were associated with parents who were unaware of their child's exposure to pornography. Multiple regression results showed that children who were living with household poverty, had a poor parent-child relationship, spent much time using a smartphone/tablet, and with parents who were unaware of their exposure to violence/pornography on mobile devices were more likely to have emotional and behavioral problems.
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Literatura Erótica , Exposição à Violência/estatística & dados numéricos , Relações Pais-Filho , Psicologia da Criança , Smartphone , China , Humanos , Pais , Inquéritos e QuestionáriosRESUMO
BACKGROUND/PURPOSE: Rapid and accurate identification of pathogens and their antibiotic resistance directly from flagged blood cultures can aid clinicians in optimizing early antibiotic treatment and improve the clinical outcomes, especially in settings associated with high rates of bloodstream infection caused by vancomycin-resistant Enterococci (VRE) and carbapenem-resistant Enterobacteriaceae (CRE). We compared the results of the BioFire FilmArray Blood Culture Identification (BCID) panel with those of conventional methods for identifying the pathogens and their antibiotic susceptibility status. METHODS: In total, 100 randomly selected positive blood cultures (BACTEC Plus Aerobic/F bottles or BACTEC Anaerobic Lytic/10 bottles) were analyzed. The pathogen detection efficiency of FilmArray BCID panel was compared with that of conventional method using MALDI-TOF MS system (Bruker MALDI Biotyper) and susceptibility testing by the Vitek 2 system. The sequencing analysis of antibiotic resistance genes was performed for discrepant results obtained from MALDI Biotyper and Vitek 2. RESULTS: Among the 100 positively flagged blood cultures, 94% of FilmArray BCID panel results were consistent with the MALDI Biotyper results. All five VRE isolates positive for vanA/vanB genes, 10 of 12 Staphylococcus species positive for mecA gene, and only one Klebsiella pneumoniae isolate positive for K. pneumoniae carbapenemase gene (blaKPC) detected in the FilmArray BCID panel were also concordant with results by the results by conventional susceptibility testing/molecular confirmation. CONCLUSIONS: The FilmArray BCID panel results not only demonstrated good correlation with conventional blood culture identification and susceptibility results but also provided results rapidly, especially for the early detection of MRSA, VRE and blaKPC-mediated CRE.
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Bacteriemia/microbiologia , Bactérias/isolamento & purificação , Hemocultura/métodos , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Fungemia/microbiologia , Fungos/isolamento & purificação , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bacteriemia/sangue , Bacteriemia/tratamento farmacológico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Técnicas de Tipagem Bacteriana/métodos , Hemocultura/instrumentação , Fungemia/sangue , Fungemia/tratamento farmacológico , Fungos/classificação , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Humanos , Estudos Prospectivos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , TaiwanRESUMO
Multiple mechanisms contribute to cancer cell progression and metastatic activity, including changes in endocytic trafficking and signaling of cell surface receptors downstream of gain-of-function (GOF) mutant p53. We report that dynamin-1 (Dyn1) is up-regulated at both the mRNA and protein levels in a manner dependent on expression of GOF mutant p53. Dyn1 is required for the recruitment and accumulation of the signaling scaffold, APPL1, to a spatially localized subpopulation of endosomes at the cell perimeter. We developed new tools to quantify peripherally localized early endosomes and measure the rapid recycling of integrins. We report that these perimeter APPL1 endosomes modulate Akt signaling and activate Dyn1 to create a positive feedback loop required for rapid recycling of EGFR and ß1 integrins, increased focal adhesion turnover, and cell migration. Thus, Dyn1- and Akt-dependent perimeter APPL1 endosomes function as a nexus that integrates signaling and receptor trafficking, which can be co-opted and amplified in mutant p53-driven cancer cells to increase migration and invasion.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Dinamina I/metabolismo , Endossomos/metabolismo , Mutação , Proteína Supressora de Tumor p53/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Adesão Celular , Membrana Celular , Dinamina I/genética , Endocitose , Receptores ErbB/genética , Receptores ErbB/metabolismo , Retroalimentação Fisiológica , Humanos , Integrina beta1/genética , Integrina beta1/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Transporte Proteico , Transdução de Sinais , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genéticaRESUMO
Dynamin Guanosine Triphosphate hydrolases (GTPases) are best studied for their role in the terminal membrane fission process of clathrin-mediated endocytosis (CME), but they have also been proposed to regulate earlier stages of CME. Although highly enriched in neurons, dynamin-1 (Dyn1) is, in fact, widely expressed along with Dyn2 but inactivated in non-neuronal cells via phosphorylation by glycogen synthase kinase-3 beta (GSK3ß) kinase. Here, we study the differential, isoform-specific functions of Dyn1 and Dyn2 as regulators of CME. Endogenously expressed Dyn1 and Dyn2 were fluorescently tagged either separately or together in two cell lines with contrasting Dyn1 expression levels. By quantitative live cell dual- and triple-channel total internal reflection fluorescence microscopy, we find that Dyn2 is more efficiently recruited to clathrin-coated pits (CCPs) than Dyn1, and that Dyn2 but not Dyn1 exhibits a pronounced burst of assembly, presumably into supramolecular collar-like structures that drive membrane scission and clathrin-coated vesicle (CCV) formation. Activation of Dyn1 by acute inhibition of GSK3ß results in more rapid endocytosis of transferrin receptors, increased rates of CCP initiation, and decreased CCP lifetimes but did not significantly affect the extent of Dyn1 recruitment to CCPs. Thus, activated Dyn1 can regulate early stages of CME that occur well upstream of fission, even when present at low, substoichiometric levels relative to Dyn2. Under physiological conditions, Dyn1 is activated downstream of epidermal growth factor receptor (EGFR) signaling to alter CCP dynamics. We identify sorting nexin 9 (SNX9) as a preferred binding partner to activated Dyn1 that is partially required for Dyn1-dependent effects on early stages of CCP maturation. Together, we decouple regulatory and scission functions of dynamins and report a scission-independent, isoform-specific regulatory role for Dyn1 in CME.
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Vesículas Revestidas por Clatrina/metabolismo , Clatrina/metabolismo , Dinamina II/metabolismo , Dinamina I/metabolismo , Endocitose/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Células A549 , Linhagem Celular Tumoral , Clatrina/genética , Vesículas Revestidas por Clatrina/ultraestrutura , Dinamina I/genética , Dinamina II/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Microscopia de Fluorescência/instrumentação , Microscopia de Fluorescência/métodos , Ligação Proteica , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , Transdução de Sinais , Nexinas de Classificação/genética , Nexinas de Classificação/metabolismo , Coloração e Rotulagem/métodosRESUMO
Clathrin-mediated endocytosis (CME) is the major endocytic pathway in mammalian cells. It is responsible for the uptake of transmembrane receptors and transporters, for remodeling plasma membrane composition in response to environmental changes, and for regulating cell surface signaling. CME occurs via the assembly and maturation of clathrin-coated pits that concentrate cargo as they invaginate and pinch off to form clathrin-coated vesicles. In addition to the major coat proteins, clathrin triskelia and adaptor protein complexes, CME requires a myriad of endocytic accessory proteins and phosphatidylinositol lipids. CME is regulated at multiple steps-initiation, cargo selection, maturation, and fission-and is monitored by an endocytic checkpoint that induces disassembly of defective pits. Regulation occurs via posttranslational modifications, allosteric conformational changes, and isoform and splice-variant differences among components of the CME machinery, including the GTPase dynamin. This review summarizes recent findings on the regulation of CME and the evolution of this complex process.
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Clatrina/metabolismo , Endocitose/fisiologia , Complexo 2 de Proteínas Adaptadoras/química , Complexo 2 de Proteínas Adaptadoras/metabolismo , Regulação Alostérica , Animais , Clatrina/química , Vesículas Revestidas por Clatrina/metabolismo , Dinaminas/química , Dinaminas/metabolismo , Evolução Molecular , Humanos , Modelos Biológicos , Fosfatos de Fosfatidilinositol/metabolismo , Fosforilação , Conformação Proteica , Transdução de SinaisRESUMO
This study assessed the computer/mobile device screen time and eye care behavior of children and examined the roles of risk perception and parental practices. Data were obtained from a sample of 2,454 child-parent dyads recruited from 30 primary schools in Taipei city and New Taipei city, Taiwan, in 2016. Self-administered questionnaires were collected from students and parents. Fifth-grade students spend more time on new media (computer/smartphone/tablet: 16 hours a week) than on traditional media (television: 10 hours a week). The average daily screen time (3.5 hours) for these children exceeded the American Academy of Pediatrics recommendations (≤2 hours). Multivariate analysis results showed that after controlling for demographic factors, the parents with higher levels of risk perception and parental efficacy were more likely to mediate their child's eye care behavior. Children who reported lower academic performance, who were from non-intact families, reported lower levels of risk perception of mobile device use, had parents who spent more time using computers and mobile devices, and had lower levels of parental mediation were more likely to spend more time using computers and mobile devices; whereas children who reported higher academic performance, higher levels of risk perception, and higher levels of parental mediation were more likely to engage in higher levels of eye care behavior. Risk perception by children and parental practices are associated with the amount of screen time that children regularly engage in and their level of eye care behavior.
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Comportamento Infantil , Computadores , Visão Ocular , Criança , Computadores/estatística & dados numéricos , Estudos Transversais , Humanos , Poder Familiar , Inquéritos e Questionários , Taiwan/epidemiologia , Fatores de TempoRESUMO
Type I and II cytokine receptors are cell surface sensors that bind cytokines in the extracellular environment and initiate intracellular signaling to control processes such as hematopoiesis, immune function, and cellular growth and development. One key mechanism that regulates signaling from cytokine receptors is through receptor endocytosis. In this mini-review, we describe recent advances in endocytic regulations of cytokine receptors, focusing on new paradigms by which PI3K controls receptor endocytosis through both kinase activity-dependent and -independent mechanisms. These advances underscore the notion that the p85 regulatory subunit of PI3K has functions beyond regulating PI3K kinase activity, and that PI3K plays both positive and negative roles in receptor signaling. On the one hand, the PI3K/Akt pathway controls various aspects downstream of cytokine receptors. On the other hand, it stimulates receptor endocytosis and downregulation, thus contributing to signaling attenuation.
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Signaling receptors are internalized and regulated by clathrin-mediated endocytosis (CME). Two clathrin light chain isoforms, CLCa and CLCb, are integral components of the endocytic machinery whose differential functions remain unknown. We report that CLCb is specifically upregulated in non-small-cell lung cancer (NSCLC) cells and is associated with poor patient prognosis. Engineered single CLCb-expressing NSCLC cells, as well as "switched" cells that predominantly express CLCb, exhibit increased rates of CME and altered clathrin-coated pit dynamics. This "adaptive CME" resulted from upregulation of dynamin-1 (Dyn1) and its activation through a positive feedback loop involving enhanced epidermal growth factor (EGF)-dependent Akt/GSK3ß phosphorylation. CLCb/Dyn1-dependent adaptive CME selectively altered EGF receptor trafficking, enhanced cell migration in vitro, and increased the metastatic efficiency of NSCLC cells in vivo. We define molecular mechanisms for adaptive CME in cancer cells and a role for the reciprocal crosstalk between signaling and CME in cancer progression.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Cadeias Leves de Clatrina/metabolismo , Clatrina/metabolismo , Dinamina I/metabolismo , Endocitose , Receptores ErbB/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular , Invaginações Revestidas da Membrana Celular/metabolismo , Endossomos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Pulmonares/genética , Camundongos Nus , Metástase Neoplásica , Fosforilação , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Risco , Transdução de Sinais , Análise de Sobrevida , Regulação para Cima/genéticaRESUMO
Clathrin-mediated endocytosis (CME) constitutes the major pathway for uptake of signaling receptors into eukaryotic cells. As such, CME regulates signaling from cell-surface receptors, but whether and how specific signaling receptors reciprocally regulate the CME machinery remains an open question. Although best studied for its role in membrane fission, the GTPase dynamin also regulates early stages of CME. We recently reported that dynamin-1 (Dyn1), previously assumed to be neuron-specific, can be selectively activated in cancer cells to alter endocytic trafficking. Here we report that dynamin isoforms differentially regulate the endocytosis and apoptotic signaling downstream of TNF-related apoptosis-inducing ligand-death receptor (TRAIL-DR) complexes in several cancer cells. Whereas the CME of constitutively internalized transferrin receptors is mainly dependent on the ubiquitously expressed Dyn2, TRAIL-induced DR endocytosis is selectively regulated by activation of Dyn1. We show that TRAIL stimulation activates ryanodine receptor-mediated calcium release from endoplasmic reticulum stores, leading to calcineurin-mediated dephosphorylation and activation of Dyn1, TRAIL-DR endocytosis, and increased resistance to TRAIL-induced apoptosis. TRAIL-DR-mediated ryanodine receptor activation and endocytosis is dependent on early caspase-8 activation. These findings delineate specific mechanisms for the reciprocal crosstalk between signaling and the regulation of CME, leading to autoregulation of endocytosis and signaling downstream of surface receptors.