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 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
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
The study aimed to get acquainted with kindergarten teachers in the development of
emotional intelligence in children, To achieve this a study too, which consisted of 40 items,
within four areas was condncted: (managing emotions, emotional knowledge, empathy, social
networking) The study tool was applied to the sample amounting (200) teachers of the
kindergarten teachers in the province of Jerash and after analyzing the results statistically
using arithmetic averages standard deviations and variance analysis quartet the following
results were reached :
- presence of statistically significant differences at the level of (α =0,05) is attributable to the
impact of the educational level in the areas of empathy and so
Abstract
This research aims to highlight the Cooperate Governance concept and determine its accounting dimensions, especially what has connected with development the management accountant role concerning the nature, scope and its location in the organizational structure in the companies as to be complied with implementing the cooperate governance principles and mechanisms in the modern businesses environment. This research has focus on clear shortage in the management accountant role in the companies, regarding to implement the governance mechanisms, especially his role to provide the information and consultations to the internal & external parties (stakeholders) . This
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This study aims to explain the role of green target costing technique in improving the relationship with suppliers in a sample of industrial companies listed on the Iraq Stock Exchange. The descriptive analytical approach was used, where a questionnaire was designed that included a set of questions that were directed to a sample of 84 individuals including production managers, finance managers, quality managers, and purchasing managers in these companies. The study uses some statistical analyzes such as correlation analysis and regression analysis to analyze the questionnaires. The study finds a positive impact of the green target costing technique on improving the relationship with suppliers. The results indicate that the relation
... Show MoreThe 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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(2)
Faced economic units face the option of restoring the capital budget annually, and the information provided for the preparation of these budgets, including financial and non-financial aspects have an important impact in the numbers of these budgets, and these units differ in the ability of their own accounting systems to maintain this information. The aim of this research is to investigate the volume of accounting information that is relied on and the reasons for the differences between one unit and another in the various economic sectors in the Iraqi environment.
The most important results of the research is the weakness of the adoption of decision makers in the Iraqi environment and lack of sufficient attention in the decision-
... Show MoreThe 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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