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 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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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
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The research aims: to build a measure of the cognitive competence of coaches from the point of view of players of Iraqi Premier League volleyball clubs and extract scores and standard levels for it. In order to achieve the objectives of the research, the descriptive method was used using the survey method. As for the research sample, it was chosen intentionally, and was represented by volleyball players for the Premier League 2024-2025. The sample was divided into exploratory, constructive, and standardizing, and starting the construction procedures, which included finding the scientific foundations for the scale, in addition to extracting the modified standard score and levels for the sample of the main experiment for standardization. Amou
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The research aims to shed light on the Corona pandemic and its repercussions on the global economy in general, and on the activities of Iraqi economic units in particular. It also aims to show the impact of the auditor’s reporting on the effects of the Corona pandemic on economic units and its reflection on the quality of his reporting. To achieve the objectives of the research, the researcher prepared a questionnaire according to the five-point Likert scale and took into account in its preparation compatibility with the characteristics of the study community, and that the target community for this questionnaire are the economic units listed in the Iraq Stock Exchange that have complet
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The love of the world and its lusts are the head of sins and the corruptors of religion, and the one who loves and loves them who prefers them over the hereafter is one of the most pitiful of creation, and the least intelligent of them, as he prefers imagination over reality, sleep over wakefulness, fleeting shadow over eternal bliss and the mortal abode over the eternal abode, and he sold the life of eternity for the most luxurious life. In life, it is dreams and sleep or as a fleeting shadow, and as it was said: The intelligent person is not deceived.
The reason for choosing this topic is due to two things:
The first: When I contemplated the reasons for the differences and conflicts that afflicted our wounded and occupied country
The aim of the research is to study the effect of the roundhouse strategy on the achievement of fifth grade secondary school in physics and their pivotal thinking. The experiment has been applied for obtaining the data, which were processed statistically using the Statistical Package for Social Sciences, the results revealed that the students of the experimental group who studied using the roundhouse strategy was superior to the students of the control group who studied in the traditional method in the achievement exam. The results also show that there are statistically significant differences between the mean scores of the students of the experimental group and the control group in the pivotal thinking exam, in favor of the experimental gr
... Show MoreInsurance is one of effective high-impact activities in the economic and social aspects of development and that the insurance companies after the creation of stability, balance and support other sectors. The insurance of financial institutions with economic and social importance has an impact on the development and help shoulder the burden of risk and distribution. And measuring Indicators of service and cost her help in evaluating the performance and activity of insurance, and the study of sectors needed by society, institutions and individuals and development of the company. Covering all aspects of life and activity. In this study will focus on the insurance sector in the field of car accidents and so plentiful and their problems and d
... Show MoreThe emerge of capitalism beside appearing modern and contemporary political systems which had become hold out it is semi-domination on more vital space of human community life, it is through some vital apparatus, which the free market apparatus had make important one which depend on achieve the privileges of the capitalism elite whom standing on it, especially the finance elite. Thus the achievement of the profit had become the main podcasted of those elite which whom the really advancer of the Globalization system, this is which incarnated by the appears and extend of the (COVID-19) fatality pandemic in the end of last year, whereas reveals widespread of it in more than one states in the world, especially the developed coun
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Starting with a problem of the weakness of accounting disclosure in some companies administration when preparing and presenting the financial reports which are submitted to the Tax authority. This problem impacts on Tax authority performance (The effect on the quality of the performance of the tax authority), because of the lack of conviction for the information contained in those reports, and the failure to achieve accurate results in tax authority performance that leads to a negative impact on determining taxable income and affect tax revenue, as well as negative impact on determining taxable income and affect tax revenue, as well as negati
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