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 responsibility of the Central Bank through the implementation of its monetary policy to maintain the integrity and stability of the financial system and the economic system, because any shock, whether internal or external, may endanger the financial system and instability, so the research sheds light on the effectiveness of monetary policy in maintaining financial stability, The most important conclusion is that there is an increase in capital, which gives banks the possibility to face the risks to which they are exposed, as well as a rise in the total bad debts, which weakens its financial position, which constitutes a decline in the financial stability of these banks.
This research set to indicate the role of the opportunity cost in the overall economic development (human and social development) by selecting the most appropriate alternative for the growth of the country in exchange for sacrificing profit limits to achieve this growth and development of the country, especially in the present circumstances of the country and after studying the reality of the economic case for him, as the problem lies with don't selecting the best alternative that enhances the gross domestic product, which extends to promote overall economic development and revive the industrial and agricultural sectors, productivity is more like Impotent, versus sacrifice alternative consumption may bring more financially lucrative than
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The internal observing system is considered a cornerstone for the high management in all the systems. It aims at defending the things for waste and increasing efficient and application the rules and regulations and constrictions. To easier for the high management activity in the internal observing system which in presented and practiced and to what extent can depend on it. Thus it goes to evaluate the internal observing system periodically to check the weak points in that system so as the find out the mistake, in the construction of the system or mistake, by indication of the workers. The importance of this study is represented in the need of increasing the coactivity in the internal observing system so as to be in touch with the new tre
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The research aims to measure the relationship and the impact of knowledge management processes to achieve the performance of insurance service, as well as analysis of the reality of the National Insurance Company to identify the level of overall performance, and to achieve this goal, it has been the selection of knowledge management processes according to the survey prepared a supplement to the study (Qubaisi, 2002), and of the four operations (knowledge generation, and storage of knowledge, and the distribution of knowledge, and application of knowledge), which represented the independent variable, and the performance has been the use of quantitative and qualitative measures, (sales growth, customer satisfaction), which represented the
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The goal of the research is to highlight the role of the governance and its characteristics in increasing the tax outcome by implementing the laws, regulations and annual controls issued annually from the general authority for taxation for the financing of the general treasury of the state, Additional development and economic capacity, As the search shares a view of the governance and its characteristics and its ideas from increasing tax output. The analytical transparent approach was used by adopting the practice of practicalities of the general authority for tax For quotations in the senior cabinet section ,the revealing of the ongoing operations was relied on the revenue for each financial year, The tools adopted in the process of ana
... Show MoreEnvironmental education is considered as process of getting Humans in communication with this environment and all its various resources. such process requires acquiring knowledge about the environment that com help humans understand their correlative relations with the environmental elements on one hand and among the environmental elements themselves on the other . Besides, such a process requires developing human skills that help them participate in developing environmental circumstances. Therefore environmental education is responsible for perspective and cultural development that governs human behavior. Regarding their environment and stimulating tendencies and interests towards the environment , let alone helping humans acquire the c
... Show MoreThe problem of the study crystallized in the following main question: What is the role of media awareness in building the student’s personality according to the opinions of a sample of middle school students? The importance of the research derives from the importance of media awareness being an important variable in building the student’s personality. The sample size was (50) students at Al-Kadhimiya Al-Sabahiya Preparatory School for Boys. In this research, a scale was used to measure the role of media awareness in building personality through (16) items on three axes (cognitive, skill, emotional), and the validity and reliability of this scale were extracted, and the results showed the following:
The poster is one of the means which can be communicate with others through it, to transfer ideas that the designer want to focus on, for its importance to accomplish the poster. It’s a visual mean contact aim to submit an idea to the audience to get a clear idea, and that would be through the shapes and subject to submit the idea. Depend on that our goal in this study is to find out, what follows:1-Finding the relationship between the shape and the idea.And the study comes up with several results, like:1-The drawings that contain themes connected with what the designer want to achieve, through the clearness of idea and to make those elements clear by putting more elements to surround the main shape.2-To assure that the strong connecti
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This study investigates the factors that led to the outbreak of protest movements in Sudan, since Sudan’s independence in 1956 until December 2018. The study aims to identify the role of protests in bringing about political and social transformations in Sudan, besides identifying the factors that help in the success or failure of the governments that resulted from those protests, with special emphasis on the challenges of the government of the 2018 revolution. The main results of the study reveal that the December 2018 protests are the largest in term of numbers, and witness huge participation of youth and women, and the slogans raised were national and comprehensive. However, the challenges that the transitional government is going th
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