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 financial fraud considers part of large concept to management and financial corruption, the financial fraud is appeared especially after corporate, that is Emerge agency theory, that is because recognize relationship between the management company and stakeholder, that is through group from constriction in order to block the management to fraud practice, that on the basis was choose another party in order fraud this practice and give opinion on financial statement, that consider basis decision making from stakeholder to basis the report auditor about creditability this is statement that reflect real activity for the company.The Auditor in order to lead work him Full professionalism to must using group from control Techniques, that is
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The aim of studying the role of environmental taxation is to reduce or mitigate the problem of environmental pollution and obtain a clean environment. And the importance of research lies in the fact that environmental taxation is one of the basic tools to achieve environmental balance. As it is considered one of the sustainable economic tools that focuses on the concept of environmental taxes and fees. Therefore, the incentives stimulated institutions to invest in clean energy and use environmentally friendly machines. Through it, the rules of the competition are updated in favor of organizations that respect the environment so that they can obtain a green competitive advantage. And that the mai
... Show MoreCommercial banks represent the main pivot in financing national economic activity and its development. The capital represents safety margin to depositors and represents a defense line that protects bank work from dangers. Basel committee requirements represent protection and comprehensive supervision to bank activities for depositors, debtors and the bank. It provides trust in bank dealings and tackles activities of high dangers. The most prominent of these requirements are capital adequacy that concerns bank management and supervision and auditing bodies such as the central bank and protecting banks that suffer weakness in its vital important borrowing activity that reflects weakness in implementing borrowing policy .The purpose
... Show MoreThis study aimed to investigate the role of Big Data in forecasting corporate bankruptcy and that is through a field analysis in the Saudi business environment, to test that relationship. The study found: that Big Data is a recently used variable in the business context and has multiple accounting effects and benefits. Among the benefits is forecasting and disclosing corporate financial failures and bankruptcies, which is based on three main elements for reporting and disclosing that, these elements are the firms’ internal control system, the external auditing, and financial analysts' forecasts. The study recommends: Since the greatest risk of Big Data is the slow adaptation of accountants and auditors to these technologies, wh
... Show MorePreparing teacher occupies the attention of many thinkers and philosophers since the age of
kaldinics ( people of mesoptam / 2342 pH ) to the Islamic age where moslems philosophers
focus their attention on thought and philosophy where the philosophy of that teaching
depends on : teacher , student and family begin .
So , the issue of preparing and training teacher occupies the attention of education scientists
depending on his vital and important role in implementing of teaching policies in philosophies
and Islamic educational thought , therefore , the preparing and development of the teacher
regards as one of the basics of teaching development because of its importance in
development of teaching performance and th
The financial fraud considers part of large concept to management and financial corruption, the financial fraud is appeared especially after corporate, that is Emerge agency theory, that is because recognize relationship between the management company and stakeholder, that is through group from constriction in order to block the management to fraud practice, that on the basis was choose another party in order fraud this practice and give opinion on financial statement, that consider basis decision making from stakeholder to basis the report auditor about creditability this is statement that reflect real activity for the company.The Auditor in order to lead work him Full professionalism to must using group from control Techniques, that is
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ABSTRACT
The research aims to identify the role of scientific planning of inventory by determining the quantity of economic demand and the number of times of purchase and associated annual total costs to achieve a sufficient and appropriate level of inventory . The research was based on the case study methodology. Materials of increasing demand in the Institute of Technical Management and knowledge of the degree of conformity of the procurement plan with the standard indicators adopted in a scientific method ,its include economic order quantity and number of purchasing times .
one of The main results of the research was the existence of a large difference between the quantity of the economic purchase of ea
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The current research focuses on a major problem: the weak role of disclosing corporate information in the application of laws, regulations and instructions related to the application of corporate governance principles weakens the ability to protect the rights of shareholders and investors in companies listed on the Iraqi Stock Exchange and the study aims to study and analyze the role of disclosure and transparency in achieving the necessary protection to ensure the rights of shareholders. The study was applied to a sample of (42) analysis samples representing (84%) of the total questionnaires distributed to investors and shareholders in all listed companies in the Iraqi Stock Exchange. The results confirm the shareholder's right to obtai
... Show MoreThe importance of the research comes from dealing with the problem of lack of traffic awareness, which causes accidents and the occurrence of human and material losses, and the research aims to study the role of satellite channels in forming traffic awareness among the public, and a sample was chosen from Baghdad consisting of (280) individuals, male and female, and used the questionnaire tool. To obtain the data, which included several questions, the results were analyzed statistically and several results were reached, the most important of which is that there is an interest among the public in following traffic programs at a rate of one to two hours to receive information through traffic programs and to identify and apply gener
... Show MoreAbstract :
The research aims to study the basic concepts of banking productivity and discuss different approaches to study what ends to identify the most important possible standards applied to measured within the Iraqi banking environment as well as research into the causes of low and high Iraqi banking productivity and identify possible treatments to curb those reasons as to ensure the rise. And in line with the research problem, which states what is the level of productivity and what are the causes of decline and the rise in private banking research sample individually. And what the Iraqi private banks and what is the relationship between performance and the impact of productivity change in the perform
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