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 issue of the Circular Economy is not a new issue to several countries, especially the developed ones. Here in Iraq it is considered newly introduced, despite the few attempts to establish projects that concern recycling most of them were doomed to fail, due to two main reasons: the first one is the financial and administrative corruption widespread in all departments of the country, the second one is the priorities of public spending. It is well known that Iraq was subjected to two major attacks, the ISIS entry attack in 2014 to Iraq. ISIS occupied about a third of Iraqi lands which resulted in a collapse in oil prices, as Iraq depends almost entirely on oil revenues in its budget which is the second attack. This made the Iraqi governme
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The aims of research is diagnose and indicate the role of fairness in the work of accounting, which is important in reducing the unacceptable practices to manage earnings by economic units, As well as the interpretation and indicate Ethical inside in the accounting and accountants in particular practices in the area of earnings management to reduce the negative effects of the practice and display the results mentioned acts according to what is supposed to be for the purposes of service users, Researchers have identified that one hypothesis, that "Fairness of accountants in of their work accounting lead to a reduction of earnings management practices". The results suggest that the accounting practices that lead to the manipu
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he study aims to build a model that revolves around the main question of the role of strategic agility (SA) in enhancing organizational excellence (OE). For the purpose of achieving OE and to determine the extent of interest and knowledge of managers at the Midwest Refineries Company (MRC) on the theoretical and practical implications, and on the performance foundations of these two vital variables with the aim of continuous improvement. A questionnaire was used and distributed to a random sample of 54 managers in this important energy production company. The study followed the descriptive analytical approach to answer the questions raised. The study model and dimensions were built according to reference models, most notably the models (Al-
... Show MoreThe study aims to identify the role of Nizwa University in disseminating the concept of knowledge economy among students from the point of view of the faculty members. The researchers used the descriptive approach, as well as used a questionnaire consisting of (20) items distributed into (4) fields. It was administered to a sample of (93) Faculty members. The results of the study showed that the role of the Nizwa University in spreading the concept of knowledge economy among students from the point of view of the faculty members was of a moderate degree. The education and training field came first with the highest average, while the scientific research and innovation field came in the last level. There were no statistically significant d
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Purpose\The researcher paper aims to determine the impact of information technology on the job performance, for Iraq private ban as through the use of technology dimensions of job performance.
The aim of this research: this study aims to discuss the importance of information technology and its role in achieving job performance and its impact on the Iraq banking sector design/ methodology/ approach used entrance design/methodology/approach- pilot, the questionnaire was used to collect data in order to develop a model to measure reliably and correctly to the variables of information technology and job performance, and hypotheses were tested through the use of some statisti
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The tax base is one of the bases of the technical organizing of taxes, and that a good selection of the tax base effects the outcome of the tax and its fairness, and with the expansion of the tax range results a dangerous phenomenon called tax evasion, which became threaten the economies of countries and this phenomenon prevents the achievement of the state to its economic, political and social objectives which seeks to resolve this phenomenon and identifying all human and material potential and realize the real reasons that lie behind it. The researcher found that tax authorities are weak in terms of it the technical material and financial abilities, the analysis of data show that then is a significant reve
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Since cancer is becoming a leading cause of death worldwide, efforts should be concentrated on understanding its underlying biological alterations that would be utilized in disease management, especially prevention strategies. Within this context, multiple bodies of evidence have highlighted leptin’s practical and promising role, a peptide hormone extracted from adipose and fatty tissues with other adipokines, in promoting the proliferation, migration, and metastatic invasion of breast carcinoma cells. Excessive blood leptin levels and hyperleptinemia increase body fat content and stimulate appetite. Also, high leptin level is believed to be associated with several conditions, including overeating, emotional stress, inflammation, obesity,
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Abstract
quality issue is the only issue the interesting in recent years of the last century, but also came out of sync with the other issue is the issue of environment, Where they have become represent two sides of one currency, challenges faced by the world and raised by the environmental problems have made industrial organizations pay great attention to the environment by improving their environmental performance, and that's where the oil industry is one of the most dangerous industries, influential and damaging to the environment due to the organizations move away from oil for adoption The application of EMS then a tool to improve environmental performance has been chosen sam
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This paper examines the impact of the organizational culture prevailing at the university center, Ali KafiTindouf, on the quality of the educational service provided by the university center Ali KafiTindouf from the point of view of the teachers of the center. The questionnaire method was used to determine the effect between the variables studied, by the distribution of 33 questionnaires on a random sample of the study community.
The study found that the organizational culture prevailing at the university center of Ali KafiTindouf contributed to reaching higher levels in the awareness and quality of the educational service provided by the teachers of the center.<
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The research aims to shed light on the importance of forensic accounting and its role in winning compensation claims against the company because of the ability of the forensic accountant (the judicial expert) to interpret and analyze the data. The research community represents the insurance companies in Iraq. The research sample was represented by the National Insurance Company. Coverage of the theoretical and deductive approach in covering the practical side, based on the financial records of the National Insurance Company for years of research.One of the most important conclusions reached by the researchers was that forensic accounting has a role
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