The Role of the Deubiquitylase MYSM1 During Alphavirus Infection Amer Nubgan The members of the genus Alphavirus are positive-sense RNA viruses and it is one of two within the family Togaviridae. Most alphaviruses are predominantly transmitted to susceptible vertebrates by a mosquito vector. Alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly life threatening symptoms. Chikungunya virus (CHIKV) is the aetiological agent represents a substantial health burden to affected populations, with clinical symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. In recent years, CHIKV has received significant attention from public health authorities as a consequence of the dramatic emergence infections in the Indian Ocean islands and the Caribbean as well as the recent emergence of CHIKV in the Americas. Infections have also been reported around Europe such as in Italy, France and Greece. Currently, no safe, approved or effective vaccine or treatment exists for CHIKV infection. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates different kinds of cellular processes, which may be targeted by viruses to aid their replication within cells. In recent years it has been well established that both the forward reaction of ubiquitination, and the reverse reaction of deubiquitination are targeted during virus infection to enhance their replication, either by targeting of cellular proteins or encoding viral homologues of key pathway proteins. The reverse reaction is undertaken by a large family of enzymes termed deubiquitylases or DUBs, and many of these have been shown to play a crucial role, not only in virus replication but also in the regulation of the immune system and vesicle trafficking. The DUBs are attractive drug targets and have increasingly been implicated in cellular processes germane to malignancy which makes the continued characterisation of the role of DUBs during virus infection a worthwhile objective. In on-going experiments in the research group a DUB siRNA pools library screen identified 12 DUBs (USP1, USP4, USP5, USP34, USP45, USP46, OTUD6A, UCHL1, JOSD2, BRCC3 and MYSM1). Depletion of these hits in HeLa cells lead to an increase in cell viability following Semiliki Forest Virus (SFV) infection (and predicted to be pro-viral) and thus could potential be candidate antiviral targets. Inroads into understanding the role of the DUB hits during the alphavirus infection, focusing initial on the BSL2 model virus SFV, and extending this to CHIKV (at BSL3). In the present study, further screening focused on the deconvolution siRNA pools for the DUB hits. Investigation of the subsequent follow up experiments with one strong candidate DUB from this list, MYSM1. Two different approaches were taken. Firstly, the effect of depletion of MYSM1 by siRNA treatment was further investigated in HeLa cells. Secondly, the analysis was extended to investigate the role of MYSM1 in fibroblasts utilising MYSM1 genetic knockout murine embryo fibroblasts. Results from this study indicate that depletion of MYSM1 in HeLa cells by siRNAs resulted in a reduction in both SFV and CHIKV replication, as assayed by measuring RNA levels and plaque formation. It was also found that MYSM1 genetic knockout in MEF cells lead to increase in both SFV and CHIKV replication. In addition, depletion of MYSM1 by siRNAs in MRC-5 cells lead to increase in SFV replication. In conclusion, MYSM1 generated interesting data, implying a role during virus infection that appeared to depend on the cell type being infected. Up to now it is unclear what the effector mechanisms are that contribute to these observations, subject to further mechanistic and functional studies, may increase the options available for targeting this vital DUB during Alphavirus infections.
The Green Productivity topic is considered as one of the more conceptual novelty in the field of Production and Operations Management, and one of the least topics addressed in the literature competent, Green Productivity (GP) is a strategy for enhancing a business's Productivity and environmental performance at the same time, for overall socio - economic development, It is the application of appropriate techniques , technologies , and management systems to produce environmentally compatible goods and services. the research aimed to find the contribution of this concept for success the industrial Organizations.
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Abstract
The decision maker needs to understand the strategic environment to be addressed through different means and methods. It is obvious that there is a difference between the three strategic environments (conflict environment, peace environment, post- peace environment) in terms of inputs and strategies to deal with each one of them. There is an urgent need to understand each pattern separately, analyze its inputs, and identify the factors and variables that affect the continuity of this situation (conflict, peace, post-peace). It is not appropriate to identify treatment without diagnosis of the condition, so it is very important to understand the type of strategic environment to be dealt with it.
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Abstract: The international community now places significant emphasis on achieving zero carbon emissions, requiring both new researchers and experienced policymakers to prioritise this goal. This article examines the effects of carbon taxes, carbon cap and trade, renewable energy (RE) production and consumption, and economic growth (EG) on carbon emission reduction in the United States, Japan, Canada, and Australia. The study collected secondary data from the World Development Indicators (WDI) secondary source spanning the years 1991 to 2022. The study examines the relationship between variables using the cross-sectionally augmented autoregressive distributed lag (CS-ARDL) approach. The findings indicate that carbon taxes, carbon cap and tr
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The research seeks to highlight the importance of digital finance in banking by providing financial and banking services and its role in improving the access of financial services to customers at the farthest possible point by using modern technology to finance their needs by granting them cash credits through electronic payment tools to facilitate them and shorten time and effort as well as Low cost, and this cannot be achieved without concerted efforts and the provision of basic infrastructure that includes connecting the Internet to all targeted areas, whether cities or rural areas, as well as distributing the largest possible number of ATMs and sending specialized teams to those areas that develop in customers the culture of digital
... Show MoreThroughput accounting is concerned with a throughput measurement process to determine the efficiency of the company, to know the problems and obstacles it suffers from, to determine their causes and ways to address them.The research problem is represented by the following question: does the application of a throughput accounting lead to maximizing the company's profits? The aim of the research is to demonstrate the importance of throughput accounting, which is one of the tools of management accounting in providing an efficient information system that provides the company’s management with the information it needs to improve its production processes, increase a throughput, and thus maxi
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The necessity of addressing global economic prosperity has garnered significant attention from recent studies and policymakers. This article analyses the effects of the digital economy, business synergies, and trade policies on the economic prosperity of China and India. The study examines the impact of political support on the digital economy, business synergies, trade policies, and global economic prosperity in China and India. The study collects data from prominent economists in India and China using questionnaires. The article utilised the SPSS-AMOS software to analyse the relationship between variables. The results showed that the digital economy, business synergies, and trade policies are positively linked to global economic prosperit
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The present study deals with the websites of Iraqi political parties on the internet to identify the effectiveness in providing communicative applications that help audience to participate, express their opinions, their positions, and other aspects reflecting the extent of employing modern technological tools to allow opportunities for political, and democratic participation since the internet has become an effective tool for political communications of political parties. The research sample includes eight political parties. The research concludes that the Iraqi political parties do not employ interactive communication patterns to reflect their interests in communicating with the public, providing opportunities for their participation an
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Based on the theoretical review of researches and studies concerned with virtual teams in organizations, it was found that the role of virtual teams varies from case to another, and it may be positive or opposite. The purpose of the current research is to examine the role of virtual teams in the impact of cultural intelligence on the strategic excellence of Zain worldwide Group. An electronic questionnaire was designed through the (Google) and (Microsoft) forms, and distributed then on a sample of (146) participants with a high organizational level of the HRM departments within the group. The results showed that there was a positive moderator role of virtual teams in the relationship of cultural intelligence and strategic excellence
... Show MoreReducing costs and protecting the environment surrounding economic unity has become the concern of many economic units and shifting their ideas towards preserving resources and protecting the environment by adopting strategies and techniques that take into account when applied reducing production costs and protecting the environment, including these strategies and techniques, the technical costs of the product life cycle and the strategy of cleaner production, as the application of the two concepts in local economic units helps to try to keep up with the countries that work to keep up with the success of their economic units by following the concepts that have been successful in Developed countries by maintaining the sustainabilit
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