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.
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The research aims to examine the evaluation of educational quality management and the ways to improve it in the College of Education for Women at the University of Baghdad from the point of view of the academic staff. The research community consisted of (288) participants comprising all members of the academic staff in the College of Education for Women at the University of Baghdad for the academic year (2019-2020). As for the questionnaire, it was distributed to the academic staff of the scientific departments according to their affiliation for the purpose of identifying the availability of the requirements of the quality of the teaching service provided to them by the educational institution. The researcher adopted a questionnaire deve
... Show MoreThe current research aims to reveal the reality of coping the scientific research in Omani universities in the Sultanate of Oman with the requirements of the Fourth Industrial Revolution in the light of Oman’s 2040 vision. It also aims derive some suggestions to develop the scientific research in these institutions. The study has adopted a qualitative approach in which interviews were conducted. The sample consisted of (16) leaders of governmental and private higher education institutions, as well as, some experts in the field of Fourth Industrial Revolution. The theoretical significance of the study is represented by its response to Oman’s vison in 2040. It is further in line with the previous international reports and educational s
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سعي المجتمع العراقي منذ أكثر من نصف قرن مضى لإعادة استثمار عشرات المليارات من الدولارات من الإيرادات النفطية في القطاع الزراعي وهياكله وبنياته التحية، كإنشاء السدود والخزانات المائية واستصلاح الأراضي والمشاريع الإنتاجية الحيوانية والنباتية وبطاقات كادت تقترب او تتجاوز حاجز طلب السكان من الأغذية والمنتوجات الزراعية التي تغذي الصناعة الا ان الزيادة السكانية وتحسن مستوى الدخل النفطي شكلا انتقالا جدي
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The grammar structure transforms from its fundamental field to another field that takes new dimensions, and is used in another way in speech that differs from the first one, because the formula basis of the name(Faael) in speech is a (distorted characteristic), and the distorted characteristic indicates the stability and the necessity of the characterized. as this characteristic has changed from its use as a distorted characteristic which was established by the elders. to a use that differs from the first and cannot be overlooked to achieve a new purpose, to be used as plural
The governmental projects are considers the prevailing in Iraq, as most of the projects implemented by the Government, the major role played by governmental projects in the provision of services to citizens and improve the economic situation in the country in general, in addition to the huge number of these projects implemented by the governmental organizations and the large failure rates of it , and because of the fact that these projects are stumbled before they reach the stage of failure, The aim of this research to identify the main factors for the stumble projects in addition to identifying the most influential factor on the causes and consequences of it , like (cost overruns , time overruns , delay and scope
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What are the variations in the design of linear motifs Vacations?
In order to solve these problems and to reach the desired outcomes research ai
Prepositions have a key function, which is to associate parts of a sentence, called letters In addition, it adds the meanings of the verbs to the names, ie reached by them, and called by the coffin characters Qualities..
I chose to search for the meaning of the preposition "from" in Surat Maryam to know its meanings in terms of originality and expansion, so the title of the research (the meanings of preposition "from" in terms of originality and expansion in Surat Maryam model(