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.
From 1979 to 1999 several theatricl groups had produced (Mackbeth) by shakespear which were directed by different director and the role being played by different actors. So the questions are: How did those a Iraqi actors approach that character by their performance? Did they interpret the character Truelly as the poet wanted to be. The researcher aims to find out the true performance by the actor who impersonate (mackbeth) as a wicked personality, who had un rational ambition. The researcher also aims to expose the style of acting fallowed by the Iraqi actors in that play. In chapter of review of literature, The researcher discusses the weaning and procedure of the actor performance which include characterization and transformation. He a
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The role and procedures for accountability in the spending units significant impact in enhancing the results of the budget it is found by studying and comparing the results of the implementation of the budget for the research sample for a period of two years to repeat the same deviations and irregularities of Guanyin, regulations and instructions that have occurred in implementation results and two consecutive Kaltjaoz customizations and low rates of implementation and the lack of exchange of allocations Finance despite the presence budget note that such remarks are always indicate in regulatory reports, but these observations repeated Bostmr in the results of the implementation of the budget. Which clearly reflects the absence of the ro
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The study investigates the possibility of utilizing public interactive sculptures to enhance physical activity in Saudi Arabia. The paper uses a descriptive-analytical methodology to identify the characteristics of interactive sculptures promoting physical activity in public areas as follows: The size and space of the work area are appropriate to the type of physical activity that is achieved, and the importance of the work site in the city and its relation to the surrounding space, identifying participants at the same time and their relationship to ensure safe interaction, as well as the relationship between the esthetic and intellectual concept of working in the community. The study concludes that three technical proposals were present
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The research aims to demonstrate the impact of internal audit in Iraqi economic units on enhancing social performance reports, through the statistical models used, as a survey list (for the independent variant) of the search, which contains five axes of each axis, contains a set of The questions were prepared on the basis of the standards issued by the Institute of Internal Auditors (IIA) and were distributed to a sample of internal auditors, as for (for the approved variable) the researcher obtained numerical data represented by the financial statements of the research sample and used statistical models such as model (Kolmakrov-Smirnov) is a good match (goodness of fit) which assumes that the data is distributed naturally as wel
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This research aimed at studying the role of calculated knowledge an its efficiency in improving the performance especially most of the organizations are living within knowledge era which concentrate on new technology investment in different fields of modern live . Under the scientific trends towards the economy of calculated knowledge which depend basically on new computer program in order to utilize the knowledge to raise the level of work performance exploiting different resources in the best way that helps the organizations to achieve their objectives because the information technology and computer programs became a means of survival and indispensible instrument within the developed world which depend on prosperity . progress
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The study tries to answer several questions posed by the subject, one of the important: How the Internet promotes rumor? And what are the most Internet applications that promote rumor? And the practical ways to reduce these negative? Using the process of in vestige and reading theoretical heritage available in this field, and inferred the numbers and statistics marked the uses of the Internet and its applications over recent years, and the characteristics of each these tools in the field of collection, processing, and dissemination of information
The importance of operational risks increases with the increase in technological development, the development of banking operations, the extent of banking compliance, and the attempt of many banks to achieve quality in banking services. And the extent of the position occupied by Iraqi banks for banking compliance and reducing operational risks. The Basel Committee (2) paid its attention to operational risks and the interest of international banks to follow policies that work to ensure banking compliance and cover operational risks, because of its role in reducing losses due to increased costs and achieving an increase in profits. Realizing and working to confront the best possible and traditional methods, that some risks Operational problem
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As the child is growing up, he goes through different phases which will be accompanied by physical and psychological changes. These changes set the basis for processes of designing and making children's clothes which in turn give its required benefits and meet the physiological, psychological and community needs. That will help provide the child with healthy physical and psychological growth.
The aim of this research is to recognize the decoration of clothes by colors and drawings and its role in clothes' richness and children's education. The research limits are objective, The limits are for female (3-5) years old. The research was done in teaching kindergarten in the college of education for women in 2016. The researchers found many
Background: This study is to evaluate the necessity of prescribing prophylactic antibiotics for nasal packing in spontaneous epistaxis. There are few published papers of infective complications in such patients.
Methods: This prospective study analysed 149 consecutive patients admitted to AL-Kindy teaching hospital with spontaneous, epistaxis, who underwent nasal packing over 2 years period . in the first year, 78 patients received prophylactic antibiotics , In the second year 71 patients were not given prophylatic antibiotics. Exclusion criteria included antibiotics prescribed for unrelated pathology and post-operative epistaxis. Signs and symptoms of acute otitis m
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