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.
This study aims to identify the amount of the effect of the ability to learn the individuals within the organization on the accumulation of intellectual capital and the role it plays in improving the performance of the organization, and to achieve that, the researcher designed a questionnaire to collect data and information from the surveyed respondents and analyzed using SPSS software, the study concluded after testing hypotheses to have a direct impact between the capacity for organizational learning and the accumulation of intellectual capital, which in turn affects the accumulation of intellectual capital as a positive and direct impact on the performance of the organization, al
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Abstract
The objective of the research is to identify the role of innovative leadership in achieving the dimensions of administrative empowerment in the company for the public of food industries. The various variables have shown the importance of innovative leadership to achieve the dimensions of administrative empowerment in both international and local companies. Administrative Empowerment "In order to answer this question, a virtual model was developed to reflect the relationship and impact between innovative leadership and administrative empowerment. The research was based on the analytical descriptive approach. the research community, The company represented the general company for food industries, retrie
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The current study is based on previous findings, where corporate governance (CG) significantly increased corporate social responsibility (CSR) to enhance transparency while reducing the tendency of corporate management to engage in earnings management (EM). A sample of 11 Iraqi banks listed on the Iraq Stock Exchange from 2010 to 2020 was selected. The CG was included in the board size and board independence apart from the variables of Chief Executive Officer (CEOs) gender, majority shareholder ownership, foreign ownership, and institutional ownership. The CSR included the wage growth rate, bank contribution growth rate for social security, training programmes, subsidies, environmental protection, and bank compliance with the law. Specifica
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The aim of this research is to introduce agricultural insurance, to define financing in the form of salam and the role of agricultural insurance in the prevention of risks to agricultural finance operations in the form of salam by verifying the hypotheses through which to reach the results, including the imposition of risks for agricultural finance in the form of salam, The study of agricultural finance in the form of salm, the deductive approach to the development of the problem of research and hypotheses, and the inductive method to extrapolate the results through analysis and brother The researcher concluded that agricultural insurance works to bridge the risks facing agricultural finance in the form of the ladder in cases of
... Show MoreThe auditor has a role in allocating joint costs in the gas industry, and the auditor's procedures are considered as systematic critical examination, analysis and evaluation of everything related to costs in general and joint costs in the gas industry in particular, with the aim of controlling the joint costs of gas industry products, and knowing the share of the cost of each product from the total industry costs Gas products reflect the reality of the company's performance by discovering weaknesses, defects and any errors, to ensure increased effectiveness and efficiency of the parties concerned with auditing them and imposing control and control over the company's resources, as well as
... Show MoreThe current research aims to find out the role of transformational leadership in decision-making wise, to cope with the decline in some of the banking performance indicators as a result of the absence of the modern concept of the leadership of those so-called B (Transformational Leadership) and preventing benefit from the advantages in the banks, and I test the research on a sample of the Iraqi private banks through applied to a sample (77) Mdermvud and Associate Director and Advisor to the Chairman of the Department, the distributors (7) banks, and used the head of the questionnaire as a tool to collect data and information. For the purpose of access to the results, the research sought to test two hypotheses two main hypotheses sub pop
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Informativity, being an essential component of text/discourse, plays a significant role in highlighting the intended meaning and finally contributes to the overall process of rendering a text cross-culturally. It has, however, been overlooked by translators in doing their jobs. In poetic translation, informativity plays a particularly significant role as it sheds light on the ungraspable traits of meaning.
This study tries to explore this aspect in a translation of Emily Dickenson's Slant of Lights to see where the translator fell short in this aspect with attempts to produce an alternative translation taking into consideration the various orders of informativity. For this purpose, a model of informativity is forwarded t
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