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.
Recent technological developments in the mass media a major paradigm shift in important segments of society, particularly among young people in particular social networking sites including (Facebook) .
it was able to link the sprawling parts of the world and paved the way for all the communities of convergence and exchange views, ideas and desires as provided by their ability to communicate through the use of video clips,pictures,share files, chat, communicate and direct interaction between the audience for this the means. Wondered problem Find the role that can be played using the university youth to the social networking site (Facebook ) to modify their attitudes or their interest in Iraqi society issues, With focused research objec
Any design subject to a set of forces contributing to the establishment of relations working to strengthen the internal elements of the design; any imbalance in these elements can make a fragmented and weak design, thus preventing it from achieving the goal or performance. Poor performance can be attributed to various factors: the extent and function of the elements and principles in the design, realization of the idea, especially in fashion design.
Moreover, there are many aspects of a design that go into achieving the realization of the designer’s idea. The design utilizes a lot of stimulants by drawing attention to its design, which is consistent with the need for psychological and material individuals. In this research, we will
The tax exemption, whether wholly or partially, and for an unlimited duration of the investment or for a limited period of few years, is one of the encouraging things to the flow of foreign capital. And if necessary, impose tax on the profits of the invested capital, the promotion requires that not be discriminatory taxes or payments in the amount of money with the need to avoid double taxation. The tax exemption is granted by the government and the feature according to the law of a natural person or legal entity seeking from the government purports to achieve a set of political goals, economic and social development. The reduction of taxes or grants partial exemption is one of the factors that encourage attract of direct foreign i
... Show MoreThe research aims to Measuring the auditors' commitment with the analytical procedures of the economic units of the research sample in carrying out their professional duties and the importance of this commitment to the tax administration and the extent of their reliance on the external auditor's report and the financial statements in determining the income tax and its effect on the tax revenues.
The research depends on a main hypothesis stating that "The use of analytical procedures by the external auditor has a positive impact on the availability of confidence and credibility in the financial statements presented to the tax administration and has a positive impact on the tax revenues."
The resear
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the history of the Scouting movement reflects the global social cultural and technological change over more than a century. scouting aims to develop young people worldwide through educational programs based on specific principles and values. in arab countries, the scouting movement is considered one of the most important platforms contributing to developing young people and enhancing their rule. positive in society, began with the establishment of the first Scout camp in the region and witnessed great growth and prosperity over the decades the research reveals the historical roots and development of the scout movement in the leading arab countries and analyzes the positive impact of scout movement in the leading arab countries on the develo
... Show MoreChina's economic policy and its huge capabilities operate according to an expansion strategy, especially in investing foreign projects, as the past ten years have witnessed a major development in the elements of comprehensive strength, especially in the economic field, in 2014 China launched the largest initiative in the world, represented by the Belt and Road Project (BRI), which links nearly 70 countries, through this project, a very important region has emerged, which is (the port of cadres) in Pakistan, as China has headed towards that region and given the highest importance that is in its interest in the first place regardless of the great Pakistani interest, This is consistent with its future aspirations, especially after breaking
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Finance is an essential element when developing any housing policy because of its role in providing funds to institutions concerned with housing lending. Therefore, the research aims to evaluate the financial aid provided by the Central Bank of Iraq in solving the housing crisis through the adoption of the Central Bank of Iraq initiatives to support the financing of the housing sector, and here The importance of the research is highlighted to determine the role of the initiative by drawing an effective strategy aimed at providing the housing sector with the necessary funding. By providing financing to financial institutions directed towards providing real estate credit, and that the percentage of the contribution of the implement
... Show MoreMagnetosphere is a region of space surrounding Earth magnetic field, the formation of magnetosphere depends on many parameters such as; surface magnetic field of the planet, an ionized plasma stream (solar wind) and the ionization of the planetary upper atmosphere (ionosphere). The main objective of this research is to find the behavior of Earth's magnetosphere radius (Rmp) with respect to the effect of solar wind kinetic energy density (Usw), Earth surface magnetic field (Bo), and the electron density (Ne) of Earth's ionosphere for three years 2016, 2017 and 2018. Also the study provides the effect of solar activity for the same period during strong geomagnetic storms on the behavior of Rmp. F
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