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.
This research aims the effects of negative media on the educational identity of community. Whereas display the concept of educational identity and its basic components, as well as the role of educational institutions for example the school and the family in form it and reinforcing this identity to individuals. The study showcasing the harmful impact of both traditional and modern media on identity and values, spotlight several examples like the promotion of consumerism and materialism through television programs. which results in the young people to adopt materialistic values like simplicity. The study concludes that media is a double-edged weapon: it can instill virtues and support education if used duly, but it can also weaken the educat
... Show MoreThe Arabic pronouns received a lot of attention from the ancient Arab grammarians, so they explained their origins, the different forms of their structure, and the aspects of the Arabs’ use of them, and explained the aspects and reasons for these uses, with what they had of linguistic insight, which guided them to clarify the truth of these pronouns.
And recently, this research seeks new knowledge of the development of the structure of the nominative pronouns (he), (she), (them), (taa), and (waw) between dialects and towards classical Arabic, by analyzing the structure of these pronouns into their components. Its linguistic formulas are traced from the ancient Arabic texts, and by ancient I mean the texts of the era of linguistic ci
The purpose of the present study is to identify the comprehensive concept of desertion through the Holy Qur’an and to derive some educational implications related to the concept of desertion and its editing. The also aims to explain the images and forms of desertion. The researcher used the qualitative analytical method. The study concluded that the comprehensive concept of desertion was represented in moving from the country of polytheism to the country of Islam, singularity, alienation, and isolation, leaving, repelling and showing off, abandoning the wife in bed, and reciting from the Qur’an recitation, action, and arbitration, insulting, abandoning, delirium, intersection, and manipulation. The researcher has drawn many education
... Show MoreIn this paper, a new approach was suggested to the method of Gauss Seidel through the controlling of equations installation before the beginning of the method in the traditional way. New structure of equations occur after the diagnosis of the variable that causes the fluctuation and the slow extract of the results, then eradicating this variable. This procedure leads to a higher accuracy and less number of steps than the old method. By using the this proposed method, there will be a possibility of solving many of divergent values equations which cannot be solved by the old style.
Several studies have indicated that more than 600 cities in the world (intermas of rapid growth and development) will generate about 60% of international economic growth between 2010 and 2025 . by 2025 , 66% of the worlds population will live in urban areas the management of cities will face challenges that accompany this increase in the population which requires preparing to face these challenges and problems and the need to provide the aim of the research to know the readiness of Baghdad city to implement the strategies of urban management throught on asmple representing the ( Advisiry group for the comprechnsive development plan for the city of Baghdad 2030 and its supporters ) in the municipality of Baghdad and the number of
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The crystalline zeolite, namely faujasite type Y with SiO2/Al2O3 mole ratio of 5 was used as raw material for preparation of isomerization catalysts. A 0.5 wt % Pt/HY-zeolite catalyst was prepared by impregnation of the decationized HY-zeolite with chloroplatinic acid. The dectionized HY-zeolite was treated with HCl, HNO3 and HI promoters using different normalities and with different concentrations of Sn, Ni and Ti promoters by impregnation method to obtain acidic and metallic promoters' catalysts, respectively. A 0.5 wt% of Pt was added to above catalysts using impregnation method. Isomerization of n-hexane was carried out at different prepared catalysts. The isomerization temperature varied from 250–325° C over weight hourly space
... Show MoreThe research seeks to identify the factors affecting the monopoly and the possibility of measuring the phenomenon of economic ( monopolistic profit) accounted for and that the importance of research topic arising from the transformation of the majority of developing countries to the market economy, which represents the image of the capitalist economy, which is a monopoly, a stages that economy in its various forms, whether Market Worldwide sales monopoly or monopoly, which generates absolute monopolistic profits, which more or less affect on the overall economy of those countries than they should study the phenomenon of monopoly and its impact on the economies of those countries that still love to find her site reinforces its pos
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The research tagged (eloquence of the Qur’anic verses in the resurrection verses) deals with study and analysis of the aesthetics of miracles in the Qur’anic poems centered on the horrors of the Day of Resurrection, and aims to clarify the role of the Qur’anic unique and its impact the miraculousness of the Qur’anic style systems, the accuracy of the unique selection and its wonderful harmony in form and content, voice and meaning, composition And a picture with its context and denomination; based on that, the research was based on the analytical method to reach its goal, and the research plan imposed its division into two preamble and two topics, the first topic dealt with: the rhetoric of the nominal Qur’anic verses in
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The intellectual capital an important variable in the equation of the success of seeking economic units to achieve a competitive advantage, since it is a real capital for economic unity it constitutes a strategic importance as the main source to achieve high profitability in the economic unit and highlights the importance of showing intellectual capital components of the main Represent of human capital and structural capital and relational capital, through effective and the prominent role played by intellectual capital within the economic unity in order to achieve a sustainable competitive advantage contribute to attracting investors with longer investment decision of the most important and difficult decisions ta
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