RESUMO
Nervous necrosis virus (NNV) belongs to the Betanodavirus genus of the Nodaviridae family and is the main cause of viral nervous necrosis disease in marine fish larvae and juveniles worldwide. The NNV virion contains two positive-sense, single-stranded RNA genomes, which encode RNA-dependent RNA polymerase, coat protein, and B2 protein. Interestingly, NNV infection can shut off host translation in orange-spotted grouper (Epinephelus coioides) brain cells; however, the detailed mechanisms of this action remain unknown. In this study, we discovered that the host translation factor, polyadenylate binding protein (PABP), is a key target during NNV takeover of host translation machinery. Additionally, ectopic expression of NNV coat protein is sufficient to trigger nuclear translocalization and degradation of PABP, followed by translation shutoff. A direct interaction between NNV coat protein and PABP was demonstrated, and this binding requires the NNV coat protein N-terminal shell domain and PABP proline-rich linker region. Notably, we also showed that degradation of PABP during later stages of infection is mediated by the ubiquitin-proteasome pathway. Thus, our study reveals that the NNV coat protein hijacks host PABP, causing its relocalization to the nucleus and promoting its degradation to stimulate host translation shutoff. IMPORTANCE Globally, more than 200 species of aquacultured and wild marine fish are susceptible to NNV infection. Devastating outbreaks of this virus have been responsible for massive economic damage in the aquaculture industry, but the molecular mechanisms by which NNV affects its host remain largely unclear. In this study, we show that NNV hijacks translation in host brain cells, with the viral coat protein binding to host PABP to promote its nuclear translocalization and degradation. This previously unknown mechanism of NNV-induced host translation shutoff greatly enhances the understanding of NNV pathogenesis and provides useful insights and novel tools for development of NNV treatments, such as the use of orange-spotted grouper brain cells as an in vitro model system.
Assuntos
Proteínas do Capsídeo/metabolismo , Núcleo Celular/metabolismo , Doenças dos Peixes/imunologia , Nodaviridae/imunologia , Proteínas de Ligação a Poli(A)/metabolismo , Biossíntese de Proteínas , Infecções por Vírus de RNA/veterinária , Animais , Bass , Proteínas do Capsídeo/genética , Proteínas de Ligação a Poli(A)/genética , Transporte Proteico , Infecções por Vírus de RNA/imunologia , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismoRESUMO
This work demonstrates a highly sensitive pressure sensor that was fabricated using carbon microcoils (CMCs) and polydimethylsiloxane (PDMS). CMCs were grown by chemical vapor deposition using various ratios of Fe-Sn catalytic solution. The pressure sensor has a sandwiched structure, in which the as-grown CMCs were inserted between two PDMS layers. The pressure sensor exhibits piezo-resistivity changes in response to mechanical loading using a load cell system. The yields of the growth of CMCs at a catalyst proportion of Fe:Sn = 95:5 reach 95%. Experimental results show that the sensor achieves a high sensitivity of 0.93%/kPa from the CMC yield of 95%. The sensitivity of the pressure sensor increases with increasing yield of CMCs. The demonstrated pressure sensor shows the advantage of high sensitivity and is suitable for mass production.
RESUMO
BACKGROUND: Healthcare professionals in Taiwan are exposed to a myriad of occupational health and safety hazards, including physical, biological, chemical, ergonomic, and psychosocial hazards. Healthcare professionals working in hospitals and healthcare facilities are more likely to be subjected to these hazards than their counterparts working in other areas. OBJECTIVES: This review aims to assess current research literature regarding this situation with a view to informing policy makers and practitioners about the risks of exposure and offer evidence-based recommendations on how to eliminate or reduce such risks. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses review strategy, we conducted a systematic review of studies related to occupational health and safety conducted between January 2000 and January 2019 using MEDLINE (Ovid), PubMed, PMC, TOXLINE, CINAHL, PLOS One, and Access Pharmacy databases. RESULTS: The review detected 490 studies addressing the issue of occupational health and safety hazards; of these, 30 articles were included in this systematic review. These articles reported a variety of exposures faced by healthcare professionals. This review also revealed a number of strategies that can be adopted to control, eliminate, or reduce hazards to healthcare professionals in Taiwan. CONCLUSION: Hospitals and healthcare facilities have many unique occupational health and safety hazards that can potentially affect the health and performance of healthcare professionals. The impact of such hazards on healthcare professionals poses a serious public health issue in Taiwan; therefore, controlling, eliminating, or reducing exposure can contribute to a stronger healthcare workforce with great potential to improve patient care and the healthcare system in Taiwan. Eliminating or reducing hazards can best be achieved through engineering measures, administrative policy, and the use of personal protective equipment. IMPLICATIONS: This review has research, policy, and practice implications and provides future students and researchers with information on systematic review methodologies based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses strategy. It also identifies occupational health and safety risks and provides insights and strategies to address them.