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 experiment was condncted in greenhouse of Botanical Garden at Biology Garden Dept,College of Education for Pure Science (Ibn-Al-Haitham),University of Baghdad , during the growing season 2013-2014 to study the role of salcylic acid in three concentrations (0.12and24) ppm and two levels of NPKZn fertilizer ( 0. 160) kg.H‾1 and four concentrations of sodium chloride (0.50.100and150) Mmol and the intreaction between salcylic acid and NPKZn on some of morphological parameters of Allium cepa. The experiment was performed with random compelete block design (RCBD)with three replications and the results showed the
... Show MorePurpose :This study seeks to provide the point of view stands on the marketing performance of the banks in the context of Dynamic Equilibrium of marketing. It aims to develop a prototype of measuring marketing performance under the umbrella of marketing dynamic prototype, embodied of the strategic alliance and competition, and the laws and legislation, and to explore any of the dimensions more effective in achieving performance. This study aims to discusses the importance of the Dynamic Equilibrium of marketing and it role in achieving the marketing performance <
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Background and Aim: The aryl hydrocarbon receptor (AhR) plays a pivotal role in spermatogenesis through its regulatory functions in redox balance and gene expression. This study aimed to investigate the effects of resveratrol (RES), a polyphenolic AhR modulator, and CH223191, a selective AhR antagonist, on male reproductive function in rats by assessing sperm quality, oxidative stress, testicular histopathology, and AhR gene expression. Materials and Methods: Forty adult male rats were randomly divided into four groups: (i) Control, (ii) dimethyl sulfoxide (vehicle), (iii) RES (100 mg/kg i.p., twice weekly), and (iv) AhR⁻ (CH223191, 10 mg/kg i.p., twice weekly), treated for 60 days. Post-treatment, sperm motility, survival, viabi
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This research aim at finding out the impact of using the strategy of shape V on the achievement of the students of the Department of Artistic Education in the subject of "Principles of scientific Research ". This strategy is one of the cognitive strategies used in this topic . To verify the aim of the research ,the two researchers have put the following null hypothesis:-There are no significant differences on the level of 0,05 among the average degrees of the students of the experimental group in their answers on the topics of the pre and post cognitive achievement tests of the subject of "principles of scientific Research " . The two researchers have adopted the experimental approach which consists of one group . the population of the r
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An experiment in the semester, the second semester of the academic year (2022-2023), and the data used was not processed (the second test for two independent, inaccurate samples, the Bermon correlation coefficient, and the Spearman correlation coefficient), and the following results were reached: There is a statistically significant difference at the level of ( 0) average, 05) between the third grade who studied the plan for asking cluster questions, and between the average of those who studied the special feature according to the traditional method of selecting achievement, and enjoyed completing the specialization, choosing the experimental group, because the strategy of asking cluster questions is one of the externalities that... Lear
... Show MoreThis research deals with number of novels for Marguerit Doras , specially A Bridge Towards Basfic and The Lover . we specialize the first chapter for discussing a very important issue , which is the Maraguerit Doras novelist world in another word the most important themes . that we discuss and through that we tried to clerify the privacy the characters of Marguerit Doras in comparative with her own generation and in the second chapter we discussed the most important characteristics of the romantic hero spedially the characteristics of women in her novels.
The aim of this research is to identify the strengths and weaknesses of organizational health in the Iraqi Central Handball Federation from the point of view of those who manage the implementation of the annual curriculum, and adopt a descriptive approach in the method of studying the case. This is based on a sample of administrators of the Iraqi Handball Federation curriculum [trainers, governors, members, president, the 138 members of the Central Federation's Administrative Authority, the President, members of the sub-federations of the sports market (2021/2022) selected deliberately by 100% and then divided into statistical analysis sample (30), reconnaissance sample (10), and application sample (98)]. The regulatory health questionnaire
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The Internet has added another dimension to public relations in institutions and organisations, as it provided tools and communication channels, especially social networking sites, which provided information and data on public relations for the institution through these websites. In addition to its communication with its audience, and the audience's interaction with it, so our research tagged (the effectiveness of public relations of the Sunni Endowment Diwan through social networking sites): An analytical study of the official Facebook page of the Diwan that addresses the knowledge and monitoring of the contents of the official Facebook page that public relations adopt in providing information, data, and activities of the Sunni End
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The research aims to identify ways of upgrading the quality level of university education at the Middle Technical University in light of its application for the National Ranking project for the quality of Iraqi universities in order to obtain advanced grades among the Iraqi universities , Which is qualified to enter the Ranking of universities worldwide, through displaying the mechanism of the Application of National Ranking project for the quality of Iraqi universities in the Middle Technical University and its formations consisting of (5) technical colleges and (11) technical institute.
The results of the application showed several observations: The most
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The path and its nodal purposes
Abstract
This study has come to indicate the doctrinal purposes of faith in this path، It was composed of an introduction and four demands، as follows:
The first requirement: the intentions of distinguishing between the ranks of people according to divine justice، as those who pass by him are different. Some of them are safe by his work، surviving from the fire، and some of them are not peace، he falls into the fire of Hell، and all of them are different in their ranks in a manner consistent with the justice of God Almighty and the works they have given themselves.
The second requirement: the purposes of divine mercy in honoring the Prophet and his nation on the path and embodying their