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 research aims to shed light on the importance of forensic accounting and its role in winning compensation claims against the company because of the ability of the forensic accountant (the judicial expert) to interpret and analyze the data. The research community represents the insurance companies in Iraq. The research sample was represented by the National Insurance Company. Coverage of the theoretical and deductive approach in covering the practical side, based on the financial records of the National Insurance Company for years of research.One of the most important conclusions reached by the researchers was that forensic accounting has a role
... Show MoreThis 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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This paper examines the impact of the organizational culture prevailing at the university center, Ali KafiTindouf, on the quality of the educational service provided by the university center Ali KafiTindouf from the point of view of the teachers of the center. The questionnaire method was used to determine the effect between the variables studied, by the distribution of 33 questionnaires on a random sample of the study community.
The study found that the organizational culture prevailing at the university center of Ali KafiTindouf contributed to reaching higher levels in the awareness and quality of the educational service provided by the teachers of the center.<
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Abstract
quality issue is the only issue the interesting in recent years of the last century, but also came out of sync with the other issue is the issue of environment, Where they have become represent two sides of one currency, challenges faced by the world and raised by the environmental problems have made industrial organizations pay great attention to the environment by improving their environmental performance, and that's where the oil industry is one of the most dangerous industries, influential and damaging to the environment due to the organizations move away from oil for adoption The application of EMS then a tool to improve environmental performance has been chosen sam
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The banking sector of all kinds is the backbone of the economy in all countries, as it is the main financier of most economic projects in order to achieve economic development and achieve stability, which contributes to providing the necessary resources in return for obtaining a profit margin in exchange for giving up his money and bearing credit risks. Among the aforementioned banking sectors are: Islamic banks that invest their capital in several forms in order to obtain profits that enable them to continue and grow, and the most important of these formulas is the Murabaha formula, which is summarized by the bank selling a commodity after owning it and then selling it to the applicant for this commodity based on a prior request
... Show MoreSince cancer is becoming a leading cause of death worldwide, efforts should be concentrated on understanding its underlying biological alterations that would be utilized in disease management, especially prevention strategies. Within this context, multiple bodies of evidence have highlighted leptin’s practical and promising role, a peptide hormone extracted from adipose and fatty tissues with other adipokines, in promoting the proliferation, migration, and metastatic invasion of breast carcinoma cells. Excessive blood leptin levels and hyperleptinemia increase body fat content and stimulate appetite. Also, high leptin level is believed to be associated with several conditions, including overeating, emotional stress, inflammation, obesity,
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Abstract:
Purpose\The researcher paper aims to determine the impact of information technology on the job performance, for Iraq private ban as through the use of technology dimensions of job performance.
The aim of this research: this study aims to discuss the importance of information technology and its role in achieving job performance and its impact on the Iraq banking sector design/ methodology/ approach used entrance design/methodology/approach- pilot, the questionnaire was used to collect data in order to develop a model to measure reliably and correctly to the variables of information technology and job performance, and hypotheses were tested through the use of some statisti
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Abstract:
The tax is one of the elements of the general revenues of the state and contributes to covering its expenses. Taxes are imposed in most countries of the world. The tax proceeds depend on a set of factors that contribute either positively or negatively to the tax share by increasing or decreasing it. Therefore, the research aims to demonstrate the role of the tax examiner's procedures in achieving the validity of the taxable base and its reflection on the tax proceeds, as well as reviewing the tax examiner's procedures related to the tax return process. Examination and tax audit of the financial statements, as well as presenting the financial statements to an independent and i
... Show MoreThe present study was designed to investigate the effects of VêO® premium and vitamin C (Vit. C) supplementation on lipid profile before and during pregnancy in local Iraqi ewes during heat stress. The study was conducted in a private field in Fallujah city, west Iraq, during the period from 6/8/2019 to 8/2/2020. Twenty local Iraqi ewes were divided randomly into four equal groups (5 for each group) The first group (T1) was given VêO® premium (4 g/ ewe/ day), the second group (T2) was given VêO® premium (2 g/ ewe/ day), and the third group (T3) was given Vit. C (40 mg/ ewe/ day), and the fourth group (T4) was left without treatment, as a control group. Aft
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