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 current study aimed to identify the role of the theatrical technical supervisor in developing and enhancing the skills of middle school students in Baghdad. The sample consisted of 73% of the original community of theatrical technical supervisors, randomly selected from those working in the first, second, and third educational directorates in the Rassafa and Karkh areas. The sample size was 32 theatrical technical supervisors. The study used a questionnaire to collect data on three axes: the cognitive skills developed by the theatrical technical supervisor, the voice and speech skills developed by the supervisor, and the body movement skills developed by the supervisor. The results showed that the theatrical technical supervisor play
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The role of the ABC system in determining the costs of services in Iraqi banks
This research aims to clarify the role of Iraqi nature in the style of the artist Ayath Al-Doori. Through it, the spotlight was shed on the aesthetic of Iraqi nature, its importance and its relationship to art, and its pioneering role in the style of the Doori artist. The research included two axes: the theoretical axis and the applied axis. The first theoretical axis deals with two topics: The first topic: the aesthetic of Iraqi nature as part of the life and methods of Iraqi artists from ancient times until today, including the periodic artist. The second topic: the league artist touched on the private life of the league artist. As for the second (applied) axis, it includes the research community, the research sample models, the resear
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The compliance is considered
This study aimed to deduce the net atrioventricular compliance which is affected the trans mitral blood flow.
This study focuses on study group of 25 patients (15 males
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The objective of this study is to enable the role of modern and advanced computerized information systems. The model or mechanism should be developed by collecting the necessary information about the taxpayers and the sources of the taxpayers' income, on the basis of which the accuracy of the inventory process will be adopted. In addition to studies related to computerized information systems and showing their importance to the tax institution. To achieve the objectives of the study and to answer its questions, the researcher relied on collecting data and information on the subject on the literature and previous studies The secondary sources, which also formed the theoretical framework of the study, were obtained either as a practical fr
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Increased the need to promote the profession of auditing, and improving the performance of the audit process, which comes through the effective implementation of its tasks, where the auditor collects the necessary data about the nature of client activity, and any other information it deems necessary to carry out the planning and development of the strategy for how to determine the procedures for implementing the audit process and the scope and timing for evidence clues in order to form an opinion technician neutral about the fairness of the financial statements, as required by the standards of the field work of the planning and supervision of the internal control and evidence to prove, but the failure of the auditor whether in th
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Abstract
The aim of the research is to clarify the requirements of the qualification of the external auditor in Iraq and the extent of their impact on the quality of the professional performance of the audit process. The research was based on analyzing the results of the questionnaire prepared for the impact of qualifications on the quality of professional performance. The researcher has reached a number of conclusions, the most important of which is that a highly qualified and unethical auditor has a greater negative impact on the quality of professional performance than those with low qualifications. The most important recommendations of the research were the need to pay
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Internal Audit is one of the most important backers of corporate governance, the researcher expanded his interest in this subject to examine the efficiency of Internal Auditors at the Arab Bank and its branches in Jordan to achieve Accountability which enhances the Corporate Governance and to identify the effect of the International Internal Audit Standards in strengthening the role of Internal Auditors in Accountability, and the effect of Attribute and Performance Standards in Accountability. The researcher applied descriptive analysis method to define the role of Internal Audit in the Arab Bank in achieving one of the basic principles of Corporate Governance assimilated in Accountability. The researcher’s sources include
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