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 aim of the research is to clarify the role of service quality through its dimensions represented by (tangibility, reliability, safety, response, empathy) in tax compliance with taxpayers, i.e. performance of the duties and obligations of the taxpayer through its dimensions (registration, accounting, payment of the amount of tax), and to know For this role, a sample was taken from the taxpayers of the branches of the General Authority for Taxes spread in the governorate of Baghdad and its affiliated districts, which amount to (15) tax branches, as (215) questionnaires were distributed to know the impressions and reactions of the taxpayers regarding the level of service quality through the aforementioned dimensions. Using the statistic
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The importance of the accounting profession in creating data and accounting information for economic resources and their sources and changes therein , through the effectiveness of this information and the degree of suitability and providing accurate and timely manner and in a form that makes it able to rationalize decisions and performance reporting , and there are several elements and behaviors control how the effectiveness of these reports and these behaviors work ethic that govern the work of management accountant when preparing performance reports , which are the ethics of the work of professional control principles and rules of accounting , legal, such as objectivity and reliability , neutrality and timeliness that must be a
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This study aimed to identify the role of digital transformation in improving the quality of the internal audit process. The researchers used the descriptive analytical approach, and the questionnaire was relied on as a study tool that was applied to the study population consisting of internal auditors working in banks listed on the Palestine Stock Exchange, and their number was (85). A checker and a comprehensive inventory method was used due to the small size of the community, where the response data of the questionnaire was analyzed and interpreted using the Statistical Packages Program (SPSS).
The results of the study showed that the use of digital transformation contributes to ensuring the quality of
... Show MoreAbstract : This research has tackled about the role of Russia in the international policies which concerning with energy , So the most important states in the world that possesses huge energy resources to be more able in the control over the reality and future production programs and the distribution of global energy alike , the latter had effectively influence on the economic and developmental aspects within many countries in the world and its impacts on political decisions and perhaps effected too much in the dimensions of strategic policies . In this context of research , Russia has been developed a high energy policy of strategic planning in order to restoring Russia position and its global role by using its potential powerful streng
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This study aims to identify the concepts of financial crisis and its reasons of creation , also explain the effects of the accounting disclosure and the International Accounting Standards in current financial crisis, In addition to, indicate the role of accounting in the reform of the financial system from the impact of financial crisis.
The methodology of this study orientied to two main aspects, the first is an identifying approach through exploring the opinion of financial experts, the second aspect is based on an analytical approach to satisfy the requirements of experts to get there opi
... Show MoreFraud crimes, which is a form of crimes against the funds in public office, is one of the crimes of traditional and cutting-edge in the same time, but it took a distinct character from other traditional crimes because of what is based upon, behavioral fundamentals and foundations and expressive image of personal qualities, concentrated in the mental work, the inventive sophistication, and skillful abilities of the perpetrators of these crimes, in addition to what is owned by crooks today a behavioral ability represented in underestimating laws and instructions. Fraud is considered one of the organized crime methods It is the most important method of its methods, all crimes practiced by the cro
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The study deals with an analysis of the contents of the publications of the campaign (Together to defeat Corona), which was established by the United Nations Development Program in Iraq in the face of the Covid 19 virus.The research problem raises a main question:What are the implications of the campaign (Together to defeat Corona) of the United Nations Development Program (Iraq office) in addressing the Covid-19 virus in Iraq?From this main question, several sub-questions emerged, which were answered by this study in its chapters and investigations, including regarding the contents of advertisements, photos and videos for the publications of the (Together to Defeat Corona) campaign for the United Nations Iraq Office on their Facebook pageA
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