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.
Shmuel Yosef Agnon, a well-known Jewish writer, wrote many literary works, including poetry, story, etc. In the field of story, this writer used two areas: the first: a simple exterior, and the second: an inner full of secrets and mysteries. This area is common when Agnon is affected by his symbolic method of purpose. In his productions, we find the political and historical significance embodied in his characters, where there is almost no story without it.
Agnon and all his productions gave the character a large area, Agnon’s characters often play the center and cornerstone in those productions, where the author dealt deeply and stated the fines details of the external and internal of that ch
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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.
The research addresses the role of the digital economy in the growth of the Iraqi economy during the period from 2010 to 2022. The research is based on the hypothesis that the digital economy has become one of the primary growth drivers worldwide and has a close relationship with economic development. Therefore, the digital transformation in Iraq can accelerate bridging developmental gaps with other countries.
It has become evident that the Iraqi economy suffers from structural imbalances for various reasons, hindering economic growth. These reasons include political and economic factors, as well as the absence of a well-thought-out policy to promote the agricultural sector, which is considered one of the fundamental sectors capa
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Psychological aspects are a major influence and motivation factor in many cinematic and television works such as television series. There are many films that dealt with psychological issues through the personality affected by psychological projections and complexes that lead towards abnormal behavior and actions in most cases, so the researchers chose the title and the research problem was raised through the following question: What is the mechanism that fulfills a psychological role in the narrative film? The objectives of the research were to reveal the mechanism used to instill psychological contents in the feature film? As for the limits of the research, it was an intentional sample, and the researchers adopted the descriptive anal
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The aim of the study is to examine the challenges of financing small and medium enterprises in Iraq and subsequently to proffer solutions to mitigate problems. These solutions are achieved by focusing on the role of accounting information on the financial projects in for example, hotel construction, and by providing the necessary accounting information for the concerned parties to finance these projects. In order to highlight the challenges associated with the funding of small and medium enterprises and the role of accounting information in reducing those challenges, a questionnaire was prepared. As the government authorities are the ones responsible for the accomplishment of these projects, a questionnaire form was distributed in the proje
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This study deals with the role of compensation system in improving the quality of educational services (University of Halabja as a Model) also our problem was the following question ; What is the role of compensation system in its different dimensions in improving the quality of educational services? And what is the relationship and impact of using the dimensions of the compensation system to improve the quality of educational services? The hypothesis of the research included the correlation and the impacts between the compensation system and its combined variables in the quality of educational services. This was proved through a field study and the distribution of questionn
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The phenomenon of terrorism is one of the most serious challenges facing the world at present. So this concept has occupied a great deal of interest of researchers and scholars in the relevant disciplines. There is no doubt that the study of the concept of terrorism requires a study of its various aspects. However, this study will be limited to knowing the role of television channels in providing the public with information about terrorist events, the extent to which young people rely on these channels to shape their attitudes towards terrorism issues. This study also seeks the relationship between satellite television channels and terrorism based on the relevant media li
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The aim of the research is to demonstrate of the relation and the influence of the components of economic intelligence (strategic alertness, information security policy, impact policy) in achieving of economic growth (creativity, competitiveness, quality improvement). The questionnaire was used as a main tool for selected sample. Answers analyzed by using the statistical program (SPSS) to calculate the arithmetic mean, standard deviation, weight percentage, correlation, F test, and Squared factor (R2).
The research derived its importance from the distinguished role of information systems in the work of industrial companies, and its impact toward achieving economic growth rates in its various activities. T
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The traditional method adopted in the preparation of the general budget in Iraq is not consistent with developments in the size specification response and spending and the associated weakness in the size of the amounts earmarked for investment projects which could adversely affect future generations and not to enable them to continue the development, which requires talking to estimate the adoption of style public expenditure in the state budget and reduce waste and extravagant where and invest public revenues of the state in investment projects and preservation of the environment and natural resources in order to ensure the benefit of future generations system, according to the system serves to achieve the overwhelming majority of member
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